{"gene":"KDM5B","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2007,"finding":"PLU-1/KDM5B is a histone demethylase that directly removes the trimethyl mark from H3K4 (H3K4me3), demonstrated by in vitro biochemical demethylation assays and active-site mutagenesis of the JmjC domain.","method":"In vitro histone demethylation assay, JmjC domain mutagenesis, mass spectrometry","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with mutagenesis confirmed in two independent 2007 papers (PMID:17363312 and PMID:18048344), replicated across labs","pmids":["17363312","18048344"],"is_preprint":false},{"year":2007,"finding":"KDM5B demethylase activity requires the JmjC domain and uses Fe(II) and alpha-ketoglutarate as cofactors, classifying it as a 2-oxoglutarate-dependent dioxygenase.","method":"In vitro biochemical assay with cofactor supplementation and chelation; JmjC domain mutagenesis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro biochemical reconstitution with cofactor dependency confirmed; replicated across multiple papers","pmids":["18048344"],"is_preprint":false},{"year":2007,"finding":"KDM5B associates with the androgen receptor (AR) and regulates its transcriptional activity, demonstrated by co-immunoprecipitation and reporter assays.","method":"Co-immunoprecipitation, transcriptional reporter assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP plus reporter assay, single lab, replicated in a separate study (PMID:23907094)","pmids":["18048344"],"is_preprint":false},{"year":2010,"finding":"PARP-1 inhibits KDM5B demethylase activity by PARylating KDM5B and excluding it from promoters, thereby protecting H3K4me3 marks and maintaining a permissive chromatin environment for transcription.","method":"ChIP, RNAi knockdown, PARylation assay, promoter occupancy analysis","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal ChIP and functional RNAi with defined molecular outcomes, multiple orthogonal methods in a single rigorous study","pmids":["20832725"],"is_preprint":false},{"year":2003,"finding":"KDM5B (PLU-1) interacts directly with developmental transcription factors BF-1 and PAX9 via a conserved VP motif in those proteins; this interaction requires specific residues in the VP motif (demonstrated by site-directed mutagenesis) and enhances transcriptional repression.","method":"Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis, reporter assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid confirmed by co-IP and mutagenesis, single lab with multiple methods","pmids":["12657635"],"is_preprint":false},{"year":2007,"finding":"KDM5B directly represses target genes including BRCA1 and metallothionein genes (MT1H, MT1F, MT1X) by binding their promoters and reducing H3K4me3 levels, demonstrated by ChIP and siRNA knockdown with microarray analysis.","method":"Chromatin immunoprecipitation (ChIP), microarray, RNAi knockdown, overexpression","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — ChIP confirmed direct promoter binding, H3K4me3 changes measured, and microarray used to identify targets; replicated across multiple studies","pmids":["17709396"],"is_preprint":false},{"year":2007,"finding":"KDM5B binds CG-rich DNA through its ARID domain, with the GCACA/C motif identified as a consensus binding sequence.","method":"EMSA, mutagenesis, reporter assay","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — DNA binding demonstrated biochemically with motif identification by mutagenesis, single lab","pmids":["17709396"],"is_preprint":false},{"year":2007,"finding":"KDM5B directly interacts with class I and class IIa histone deacetylases (HDACs), with two PHD domains of KDM5B binding a domain in the 5' region of HDAC4 overlapping the MEF-2 binding region.","method":"Co-immunoprecipitation, domain mapping, co-localization in MAD bodies upon co-transfection","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding demonstrated with domain mapping and co-IP, single lab with two methods","pmids":["17373667"],"is_preprint":false},{"year":2011,"finding":"KDM5B is a physical component of the LSD1/NuRD complex; KDM5B and LSD1 act sequentially and coordinately to demethylate H3K4, repressing the CCL14 chemokine pathway to suppress angiogenesis and metastasis in breast cancer.","method":"Co-immunoprecipitation, ChIP, genome-wide transcriptional analysis, in vivo xenograft","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — complex membership confirmed by Co-IP, ChIP confirms promoter occupancy, functional in vivo validation; multiple orthogonal methods","pmids":["21937684"],"is_preprint":false},{"year":2014,"finding":"KDM5B PHD1 finger binds unmodified histone H3 (H3K4me0) with high specificity, whereas PHD3 finger preferentially binds H3K4me3; PHD1-H3K4me0 interaction is essential for KDM5B's role in inhibiting cell migration.","method":"Peptide pulldown, histone binding assays, domain mutagenesis, RNA-seq, migration assay","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro histone binding reconstitution with domain mutagenesis and functional validation in cell migration assay; multiple orthogonal methods","pmids":["24412361"],"is_preprint":false},{"year":2014,"finding":"KDM5B associates with components of the NuRD complex (including HDAC1) and cooperates with HDAC1 for gene repression, demonstrated by biochemical co-immunoprecipitation.","method":"Co-immunoprecipitation","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP, consistent with prior NuRD complex evidence from other studies","pmids":["24412361"],"is_preprint":false},{"year":2011,"finding":"KDM5B is recruited to intragenic regions via interaction with the chromodomain protein MRG15, which recognizes H3K36me3; KDM5B depletion leads to increased intragenic H3K4me3 and cryptic intragenic transcription, impairing transcriptional elongation of self-renewal genes.","method":"ChIP-seq, Co-immunoprecipitation, RNAi knockdown with RNA-seq, H3K36me3 interaction assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal ChIP-seq and Co-IP with defined functional consequences, multiple orthogonal methods in one study","pmids":["21448134"],"is_preprint":false},{"year":2011,"finding":"Jarid1b/KDM5B localizes predominantly to transcription start sites of developmental regulator genes; its depletion leads to global increases in H3K4me3 and failure to silence lineage-inappropriate genes during ESC neural differentiation.","method":"Genome-wide ChIP-seq (location analysis), RNAi knockdown, differentiation assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide ChIP-seq with functional KD and differentiation readout; replicated in multiple ESC papers","pmids":["22020125"],"is_preprint":false},{"year":2014,"finding":"KDM5B co-localizes with H3K4me3 at promoters and enhancers of active genes; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, linking KDM5B to focusing of H3K4 methylation.","method":"ChIP-seq, RNAi knockdown","journal":"Genome biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq with KD phenotype, multiple functional outcomes, single lab","pmids":["24495580"],"is_preprint":false},{"year":2014,"finding":"KDM5B becomes enriched at DNA double-strand break (DSB) sites in a PARP1- and macroH2A1.1-dependent manner, and is required for efficient DSB repair and for recruitment of Ku70 and BRCA1 to damage sites.","method":"Laser micro-irradiation, immunofluorescence, RNAi knockdown, γH2AX foci, clonogenic survival","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization to damage sites with functional readout (recruitment of Ku70/BRCA1), multiple methods in one study","pmids":["24778210"],"is_preprint":false},{"year":2012,"finding":"Jarid1b/KDM5B is a component of the Rb pathway: depletion of Jarid1b phenocopies Rb1 knockdown, and Jarid1b associates with E2F-target gene promoters during senescence to mediate H3K4 demethylation-dependent gene silencing.","method":"Functional genetic screen for senescence bypass, RNAi, ChIP, E2F-target promoter analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis by genetic screen plus ChIP, single lab with two orthogonal methods","pmids":["22615382","21980403"],"is_preprint":false},{"year":2012,"finding":"KDM5B forms a ternary complex with TFAP2C and Myc at the CDKN1A proximal promoter; all three factors collaborate for optimal CDKN1A repression, which requires the AP-2 binding site at -111/-103 and KDM5B demethylase activity.","method":"Co-immunoprecipitation, ChIP, luciferase reporter assay, domain mapping, demethylase-dead mutant","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP confirmed ternary complex, ChIP confirmed promoter occupancy, demethylase-dead mutant validates catalytic requirement; multiple orthogonal methods","pmids":["22371483"],"is_preprint":false},{"year":2016,"finding":"Crystal structures of the catalytic core of human KDM5B in complex with three distinct inhibitor chemotypes revealed the 2-oxoglutarate binding site geometry and selectivity determinants; KDM5B active site shares hybrid features with KDM4 and KDM6 families.","method":"X-ray crystallography, in vitro enzymatic inhibition assays, cellular H3K4me3 elevation","journal":"Nature chemical biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structures with functional validation by inhibitor biochemistry and cellular assay; single lab but multiple co-crystal structures","pmids":["27214403"],"is_preprint":false},{"year":2012,"finding":"Recombinant KDM5B catalytic core demethylates H3K4me3 and H3K4me2 in vitro with an apparent Km of 0.5 µM for H3K4me3 peptide substrate; 2,4-pyridinedicarboxylic acid (2,4-PDCA) inhibits KDM5B both in vitro and in cells.","method":"In vitro enzymatic assay with recombinant protein, kinetic characterization, cell-based inhibitor assay","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — purified recombinant enzyme with Michaelis-Menten kinetics, in vitro and cellular inhibitor validation","pmids":["22420752"],"is_preprint":false},{"year":2021,"finding":"KDM5B recruits the H3K9 methyltransferase SETDB1 to silence endogenous retroelements in a demethylase-independent manner; derepression of retroelements activates cytosolic RNA/DNA sensing and type-I interferon responses leading to tumor rejection.","method":"RNAi knockdown, Co-immunoprecipitation (KDM5B-SETDB1), MMVL30 retroelement de-repression assay, innate immune reporter assays, mouse melanoma models","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP of KDM5B-SETDB1, functional in vivo mouse melanoma models with defined immune phenotype, demethylase-independence established by catalytic mutant","pmids":["34671158"],"is_preprint":false},{"year":2010,"finding":"KDM5B acts as a corepressor for the transcription factor TIEG1/KLF10; the repression domains of TIEG1 bind the C-terminus of KDM5B, and KDM5B knockdown increases Smad7 mRNA levels, linking KDM5B to TGF-β signaling repression.","method":"Co-immunoprecipitation, domain mapping, RNAi knockdown, RT-PCR","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP with domain mapping and functional RNAi knockdown, single lab","pmids":["20863814"],"is_preprint":false},{"year":2011,"finding":"FOXP3 activates target genes by recruiting MOF (histone acetyltransferase) and simultaneously displacing KDM5B (PLU-1) from promoters, increasing both H4K16 acetylation and H3K4me3.","method":"ChIP, RNAi, reporter assay, Co-immunoprecipitation","journal":"Molecular cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP confirms displacement of KDM5B upon FOXP3 recruitment; RNAi validates functional consequence; single lab with two methods","pmids":["22152480"],"is_preprint":false},{"year":2014,"finding":"KDM5B associates with PRC2 via direct interaction between KDM5B and the SUZ12 component; co-occupancy at RA-responsive genes leads to a biphasic regulatory effect on retinoic acid signaling through decoupled H3K4me3 demethylation and PRC2-antagonizing activities.","method":"Co-immunoprecipitation, in vitro pulldown, ChIP, reporter assay","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct pulldown confirms SUZ12 interaction, ChIP and reporter assays, single lab","pmids":["24619877"],"is_preprint":false},{"year":2011,"finding":"JARID1B epigenetically represses the tumor suppressor microRNA let-7e by binding to its promoter region and removing the H3K4me3 mark, leading to cyclin D1 upregulation and G1-to-S cell cycle progression in breast cancer cells.","method":"ChIP, RNAi, cell cycle analysis, luciferase reporter, RT-PCR","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP confirms promoter binding with H3K4me3 reduction, rescue experiment with let-7e inhibitor, single lab","pmids":["21969366"],"is_preprint":false},{"year":2015,"finding":"KDM5B represses H3K4me3 at the PTEN promoter, reducing PTEN transcription and thereby activating the downstream PI3K/AKT pathway to promote hepatocellular carcinoma metastasis.","method":"ChIP, overexpression, RNAi knockdown, rescue with PTEN overexpression, in vivo xenograft","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP confirms direct promoter binding with H3K4me3 reduction, pathway rescue experiment, single lab","pmids":["25909289"],"is_preprint":false},{"year":2015,"finding":"KDM5B represses expression of H3K4me2/3 at the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells; KDM5B knockdown (but not UTX or NO66 knockdown) prevents repression of this promoter, identifying KDM5B as a specific component of the epigenetic switch controlling osteoblast vs. myoblast lineage commitment.","method":"RNAi knockdown, ChIP, differentiation assays, epistasis (UTX/NO66 controls)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and specific knockdown epistasis with paralog controls, single lab","pmids":["26453309"],"is_preprint":false},{"year":2015,"finding":"USP38 deubiquitinase couples histone ubiquitination to H3K4 demethylation by interacting with KDM5B: USP38 removes monoubiquitin from H2BK120, enabling KDM5B recruitment to promoters of proinflammatory cytokine genes (Il6, Il23a); additionally, USP38 physically binds KDM5B and prevents its proteasomal degradation.","method":"Co-immunoprecipitation, ChIP, RNAi, ubiquitination assay, mouse endotoxin shock model","journal":"Advanced science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP of USP38-KDM5B complex, ChIP confirms promoter recruitment, ubiquitination assay, in vivo validation; multiple orthogonal methods","pmids":["33240782"],"is_preprint":false},{"year":2015,"finding":"SKP2 modulates JARID1B ubiquitination: TRAF6-mediated K63-linked ubiquitination reduces KDM5B demethylase activity and increases H3K4me3; SKP2 antagonizes TRAF6-mediated ubiquitination, thereby increasing KDM5B demethylase activity.","method":"Co-immunoprecipitation, in vivo ubiquitination assay, mouse knockout models, mass spectrometry","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ubiquitination assay with pathway epistasis, mouse model validation, single lab","pmids":["25596733"],"is_preprint":false},{"year":2018,"finding":"KDM5B is phosphorylated at Ser1456 by CDK1; this phosphorylation attenuates KDM5B occupancy on promoters of pluripotency genes (SOX2, NANOG), reducing their repression and modulating stem cell population in triple-negative breast cancer.","method":"Mass spectrometry phosphorylation mapping, ChIP, CDK1 kinase assay, RNAi, stem cell marker analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-identified site validated with CDK1 kinase assay and ChIP occupancy changes, single lab","pmids":["31776402"],"is_preprint":false},{"year":2018,"finding":"KDM5B demethylates H3K4 at the XRCC1 locus to facilitate XRCC1 recruitment to DNA damage sites, and HSP90 protects KDM5B from ubiquitin-dependent proteasomal degradation by forming a complex with it.","method":"Co-immunoprecipitation, mass spectrometry, ChIP, γH2AX co-localization, knockdown, HSP90 inhibitor degradation assay","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and MS identify HSP90-KDM5B complex, ChIP links H3K4 demethylation to XRCC1 recruitment, single lab","pmids":["29989047"],"is_preprint":false},{"year":2023,"finding":"In activated macrophages, KDM5B is selectively recruited to the Nfkbia (IκBα) promoter where it erases H3K4me3 and decreases chromatin accessibility, thereby suppressing IκBα expression and enabling full NF-κB activation and pro-inflammatory cytokine production.","method":"Genome-wide ChIP-seq, ATAC-seq, RNAi knockdown, mouse arthritis and endotoxin models","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq identifies Nfkbia as direct target, chromatin accessibility assay, in vivo validation in two mouse models; multiple orthogonal methods","pmids":["36914768"],"is_preprint":false},{"year":2020,"finding":"KDM5B directly binds the PIK3CA promoter and its loss results in reduced P110α and PIP3 levels; KDM5B controls PI3K/AKT hyperactivation in prostate cancer, demonstrated in Pten/Kdm5b double-mutant mouse models.","method":"ChIP, prostate-specific conditional knockout mouse model, western blot for PI3K pathway components, in vitro knockdown/overexpression","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP confirms direct promoter binding, in vivo mouse epistasis model, pathway component quantification; multiple orthogonal methods","pmids":["32868382"],"is_preprint":false},{"year":2022,"finding":"KDM5B binds to the Atf3 (ATF3) promoter and inhibits ATF3 expression by demethylating H3K4me2/3; loss of KDM5B de-represses ATF3, suppressing TGF-β-driven cardiac fibrosis.","method":"ChIP, RNAi knockdown, mouse myocardial infarction and pressure overload models, western blot","journal":"Experimental & molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP confirms direct promoter occupancy with H3K4me3 changes, two in vivo mouse models, single lab","pmids":["36481938"],"is_preprint":false},{"year":2014,"finding":"KDM5B is required for GATA3 recruitment to the Foxa1 promoter to activate Foxa1 expression; loss of KDM5B reduces FOXA1 and ERα in mammary epithelial cells, impairing ductal development.","method":"ChIP for GATA3, KO mouse model, gene expression analysis, mammary phenotyping","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP confirms GATA3 dependency on KDM5B at Foxa1 promoter, validated in KO mouse, single lab","pmids":["24802759"],"is_preprint":false},{"year":2015,"finding":"KDM5B directly demethylates H3K4me3 at the HOXA5 promoter in endothelial cells, suppressing HOXA5 expression to maintain angiogenic capacity; endothelial-specific Jarid1b knockout attenuates retinal angiogenesis.","method":"ChIP, endothelial-specific conditional KO mouse (tamoxifen-inducible), shRNA knockdown, angiogenic sprouting assay, overexpression of catalytic-inactive mutant","journal":"Arteriosclerosis, thrombosis, and vascular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP confirms direct promoter demethylation, catalytic-dead mutant validates enzymatic requirement, in vivo endothelial-specific KO; multiple orthogonal methods","pmids":["26023081"],"is_preprint":false},{"year":2015,"finding":"KDM5B inhibits IFN-β and innate cytokine production in dendritic cells upon RSV infection; conditional deletion of Kdm5b in CD11c+ DCs results in higher IFN-γ and reduced Th2 cytokines in vivo.","method":"DC-specific conditional KO mouse (Kdm5bfl/fl-CD11c-Cre), siRNA knockdown, cytokine measurement, adoptive transfer model","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-type-specific conditional KO with defined cytokine phenotype, single lab, no direct ChIP linking KDM5B to specific promoters in this context","pmids":["26083387"],"is_preprint":false},{"year":2013,"finding":"Jarid1b/KDM5B is identified as a negative regulator of hematopoietic stem cell (HSC) activity: decreased Jarid1b levels expand HSCs in vitro while preserving lymphomyeloid differentiation potential; HSC regulators (Hoxa7, Hoxa9, Hoxa10, Hes1, Gata2) are upregulated upon Jarid1b knockdown.","method":"In vivo RNAi-based functional screen, in vitro HSC expansion assay, RNA sequencing","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo functional RNAi screen with RNA-seq readout, single lab","pmids":["23777767"],"is_preprint":false},{"year":2024,"finding":"The deubiquitinase USP7 deubiquitinates and stabilizes KDM5B protein; KDM5B then reduces H3K4me3 at the ZBTB16 promoter, repressing ZBTB16 and increasing TOP2A expression to confer cisplatin resistance in nasopharyngeal carcinoma.","method":"Co-immunoprecipitation, ubiquitination assay, ChIP, shRNA knockdown, in vivo xenograft","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and ubiquitination assay confirm USP7-KDM5B interaction, ChIP confirms ZBTB16 promoter regulation, in vivo validation; single lab","pmids":["38287116"],"is_preprint":false},{"year":2022,"finding":"In AML, Kdm5b directly binds and represses stemness gene promoters; the anti-AML effect relies on KDM5B's chromatin association/scaffold functions rather than its demethylase catalytic activity, as demonstrated using catalytic mutants.","method":"RNA-seq, ChIP-seq, CUT&RUN, catalytic mutant rescue experiments, KDM5B overexpression vs depletion in AML cells","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide profiling with catalytic mutant distinguishes scaffold from demethylase function, single lab","pmids":["35217626"],"is_preprint":false},{"year":1999,"finding":"PLU-1/KDM5B protein is nuclear and localizes in discrete foci, demonstrated by transient transfection of MYC-tagged PLU-1 followed by immunofluorescence; subcellular fractionation confirmed chromatin association in somatic and meiotic cells.","method":"Immunofluorescence of tagged protein, biochemical cell fractionation","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunofluorescence and fractionation, replicated in later studies","pmids":["10336460","14579128"],"is_preprint":false},{"year":2011,"finding":"KDM5B interacts with estrogen receptor alpha (ERα) and knockdown of KDM5B in MCF-7 cells dramatically decreases estrogen-stimulated tumor growth in vivo; KDM5B also regulates ERα target gene expression (e.g., progesterone receptor).","method":"Co-immunoprecipitation (tagged ERα and JARID1B), shRNAi knockdown, in vivo xenograft","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP with functional in vivo validation, single lab","pmids":["21369698"],"is_preprint":false},{"year":2019,"finding":"KDM5B inhibits expression of miR-448 by demethylating H3K4me3 at the miR-448 promoter, which in turn upregulates YTHDF3 and ITGA6 to promote HCC progression.","method":"ChIP, luciferase reporter (YTHDF3 3'UTR), RT-qPCR, knockdown/overexpression, in vivo xenograft","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP demonstrates direct H3K4me3 demethylation at miR-448 promoter, downstream pathway validated, single lab","pmids":["33829656"],"is_preprint":false},{"year":2013,"finding":"Jarid1b/KDM5B in mouse ESCs inhibits H3K4me3 at the Kdm5b-bound Reln (reelin) promoter; depletion of Kdm5b in adult SVZ neural stem cells increases H3K4me3 at the Reln locus, upregulates Reln expression and secretion, and enhances downstream Dab1 phosphorylation and migratory behavior.","method":"ChIP (H3K4me3 at Reln promoter), shRNA knockdown, immunofluorescence, extracellular reelin ELISA, phospho-Dab1 western blot, migration assay with reelin-blocking antibody rescue","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP at specific locus, functional rescue with blocking antibody confirms mechanism, single lab","pmids":["26739753"],"is_preprint":false}],"current_model":"KDM5B (PLU-1/JARID1B) is a JmjC-domain-containing histone H3K4me3/me2/me1 demethylase that uses Fe(II) and 2-oxoglutarate as cofactors; it functions as a transcriptional repressor by directly binding gene promoters (via its ARID and PHD1/PHD3 domains that read unmodified H3K4 or H3K4me3, respectively) and erasing active H3K4me3 marks, while also participating in multi-subunit repressive complexes including LSD1/NuRD and interacting with HDACs, PRC2 (via SUZ12), TIEG1, AR, and ERα; additionally, KDM5B recruits SETDB1 to silence retroelements in a demethylase-independent scaffolding role, is regulated post-translationally by PARP1-mediated PARylation (exclusion from promoters), CDK1-mediated phosphorylation at Ser1456 (reduced promoter occupancy), USP7/USP38-mediated deubiquitination (stabilization), and TRAF6-mediated K63 ubiquitination (reduced activity), and plays essential roles in ESC differentiation, DNA double-strand break repair, hematopoietic stem cell self-renewal, innate immune regulation, and cancer cell identity."},"narrative":{"mechanistic_narrative":"KDM5B (PLU-1/JARID1B) is a nuclear, chromatin-associated histone demethylase that erases active H3K4 trimethyl marks to act primarily as a transcriptional repressor across development, stem cell maintenance, DNA repair, immune regulation, and cancer [PMID:17363312, PMID:18048344, PMID:17709396, PMID:10336460, PMID:14579128]. Its catalytic core is a JmjC-domain Fe(II)/2-oxoglutarate-dependent dioxygenase that removes H3K4me3 and H3K4me2 with high affinity, and its active-site geometry has been resolved crystallographically and exploited by selective inhibitors [PMID:17363312, PMID:18048344, PMID:27214403, PMID:22420752]. KDM5B reaches its targets through a combination of intrinsic chromatin readers and partner factors: its ARID domain binds CG-rich DNA, its PHD1 finger reads unmodified H3K4 while PHD3 reads H3K4me3, and it is directed to intragenic H3K36me3 regions via MRG15, focusing H3K4 methylation at promoters/enhancers and preventing cryptic transcription and lineage-inappropriate gene expression during ESC differentiation [PMID:17709396, PMID:24412361, PMID:21448134, PMID:22020125, PMID:24495580]. It operates within multi-subunit repressive machinery, partnering with LSD1/NuRD-associated HDACs and PRC2 (via SUZ12), and serving as a corepressor for sequence-specific transcription factors including AR, ERα, TIEG1, and a TFAP2C/Myc complex at CDKN1A [PMID:17373667, PMID:21937684, PMID:24412361, PMID:22371483, PMID:24619877, PMID:18048344, PMID:21369698, PMID:20863814]. Through promoter-specific H3K4 demethylation KDM5B represses defined targets—BRCA1 and metallothioneins, PTEN and PIK3CA to tune PI3K/AKT signaling, and developmental/lineage genes such as HOXA5, Runx2, and Foxa1—linking it to cell migration, angiogenesis, senescence, and cancer cell identity [PMID:17709396, PMID:25909289, PMID:32868382, PMID:26023081, PMID:26453309, PMID:24802759]. Beyond catalysis, KDM5B has a demethylase-independent scaffolding role, recruiting SETDB1 to silence retroelements and restrain type-I interferon responses, and supporting anti-AML stemness repression through chromatin association rather than enzymatic activity [PMID:34671158, PMID:35217626]. KDM5B is recruited to DNA double-strand breaks in a PARP1/macroH2A1.1-dependent manner to enable Ku70, BRCA1, and XRCC1 recruitment, and it shapes innate immunity by erasing H3K4me3 at Nfkbia and proinflammatory cytokine loci [PMID:24778210, PMID:29989047, PMID:36914768, PMID:33240782]. Its abundance and chromatin occupancy are tuned post-translationally by PARP1 PARylation, CDK1 phosphorylation at Ser1456, TRAF6 K63-ubiquitination, and stabilization via USP7, USP38, and HSP90 [PMID:20832725, PMID:31776402, PMID:25596733, PMID:38287116, PMID:33240782, PMID:29989047].","teleology":[{"year":2003,"claim":"Before its enzymatic role was known, KDM5B was shown to be a transcriptional corepressor recruited by developmental transcription factors, establishing it as a chromatin regulator embedded in repressive transcriptional programs.","evidence":"Yeast two-hybrid, co-IP, and VP-motif mutagenesis with BF-1 and PAX9 plus reporter assays","pmids":["12657635"],"confidence":"Medium","gaps":["No molecular activity defined at this stage","VP-motif interaction surface on KDM5B not mapped"]},{"year":2007,"claim":"The defining discovery established KDM5B as a JmjC-domain Fe(II)/2-oxoglutarate-dependent dioxygenase that directly demethylates H3K4me3, converting a transcription cofactor into a defined enzymatic eraser of an active chromatin mark.","evidence":"In vitro demethylation assays, cofactor dependency, JmjC active-site mutagenesis, mass spectrometry","pmids":["17363312","18048344"],"confidence":"High","gaps":["Genome-wide targeting rules not yet defined","Did not resolve catalytic vs. non-catalytic functions"]},{"year":2007,"claim":"Promoter-binding and direct target studies showed how KDM5B is targeted and what it represses, linking enzymatic H3K4me3 erasure to specific gene silencing including BRCA1 and metallothioneins, and to AR and HDAC corepressor partnerships.","evidence":"ChIP, microarray, EMSA/ARID motif mapping, co-IP with HDAC4 and AR, reporter assays","pmids":["17709396","17373667","18048344"],"confidence":"High","gaps":["Causality between H3K4me3 loss and repression not separated from complex effects","HDAC/AR interactions from single labs"]},{"year":2010,"claim":"Post-translational control of KDM5B was first established, showing that PARP1 PARylation excludes KDM5B from promoters to protect H3K4me3, and that TIEG1 recruits it for TGF-β-related repression.","evidence":"ChIP, PARylation assays, RNAi, co-IP and domain mapping, RT-PCR","pmids":["20832725","20863814"],"confidence":"High","gaps":["Stoichiometry and dynamics of PARylation in vivo unresolved","TIEG1 link is Medium-confidence single lab"]},{"year":2011,"claim":"Genome-scale and complex studies revealed how KDM5B is recruited and focuses H3K4 methylation, defining MRG15/H3K36me3-guided intragenic recruitment and LSD1/NuRD complex membership coupling H3K4 demethylation to repression.","evidence":"ChIP-seq, co-IP, H3K36me3 interaction assays, RNAi/RNA-seq, in vivo breast cancer xenograft","pmids":["21448134","21937684","21369698","22152480"],"confidence":"High","gaps":["Relative contributions of intrinsic readers vs. partner-mediated recruitment not quantified","ERα/FOXP3 links Medium-confidence"]},{"year":2012,"claim":"KDM5B was placed within cell-cycle/senescence control, acting in the Rb pathway at E2F targets and forming a TFAP2C/Myc ternary complex requiring its demethylase activity to repress CDKN1A.","evidence":"Senescence-bypass genetic screen, ChIP, co-IP, demethylase-dead mutant, luciferase assays","pmids":["22615382","21980403","22371483"],"confidence":"High","gaps":["Direct catalytic requirement at E2F targets not isolated","Generalizability beyond CDKN1A unclear"]},{"year":2014,"claim":"Mechanistic dissection of chromatin reading and a non-transcriptional role emerged: PHD1 reads H3K4me0 and PHD3 reads H3K4me3 to control migration, KDM5B co-localizes with H3K4me3 to focus methylation, it links to PRC2 via SUZ12, and it is recruited to DNA double-strand breaks to enable repair factor loading.","evidence":"Peptide pulldowns, domain mutagenesis, ChIP-seq, in vitro SUZ12 pulldown, laser micro-irradiation, γH2AX foci, clonogenic survival","pmids":["24412361","24495580","24619877","24778210","24802759"],"confidence":"High","gaps":["How DSB recruitment integrates with promoter functions unresolved","PRC2/GATA3 links Medium-confidence single labs"]},{"year":2015,"claim":"ESC/differentiation and tissue-specific roles consolidated KDM5B as a lineage gatekeeper and oncogenic node, demethylating H3K4 at developmental loci (HOXA5, Runx2, Reln) and at PTEN to drive PI3K/AKT-dependent cancer phenotypes, with additional ubiquitin-based regulation by TRAF6/SKP2.","evidence":"Conditional KO mice, ChIP, catalytic-inactive mutants, angiogenic/differentiation assays, in vivo ubiquitination assays","pmids":["22020125","26023081","26453309","26739753","25909289","25596733"],"confidence":"High","gaps":["Tissue-specific targeting determinants not unified","Several cancer target links are Medium-confidence"]},{"year":2016,"claim":"Structural and kinetic characterization of the catalytic core defined the 2-oxoglutarate binding site and selectivity determinants and enabled selective inhibitors, providing a chemical-biology framework for the enzyme.","evidence":"X-ray co-crystal structures with three inhibitor chemotypes, enzymatic inhibition, kinetic characterization, cellular H3K4me3 assays","pmids":["27214403","22420752"],"confidence":"High","gaps":["Full-length regulatory domain architecture not captured","Structures of chromatin-bound complex absent"]},{"year":2021,"claim":"A demethylase-independent scaffolding function was established, with KDM5B recruiting SETDB1 to silence retroelements and suppress type-I interferon responses, expanding its role beyond catalysis into immune evasion.","evidence":"Co-IP, retroelement de-repression, innate immune reporters, catalytic mutant, mouse melanoma models","pmids":["34671158"],"confidence":"High","gaps":["Mechanism of SETDB1 recruitment domain mapping incomplete","Interplay between catalytic and scaffold modes in same cell unresolved"]},{"year":2023,"claim":"Innate immune and inflammatory roles were mechanistically anchored, with KDM5B erasing H3K4me3 and reducing accessibility at Nfkbia to enable NF-κB activation, and USP38-coupled recruitment to cytokine promoters, defining its pro-inflammatory chromatin function.","evidence":"ChIP-seq, ATAC-seq, RNAi, ubiquitination assays, mouse arthritis/endotoxin/RSV models","pmids":["36914768","33240782","26083387"],"confidence":"High","gaps":["How a repressor of IκBα coexists with cytokine-promoter recruitment context-dependently unclear"]},{"year":2024,"claim":"Deubiquitinase-mediated stabilization linked to therapy resistance was established, with USP7 stabilizing KDM5B to repress ZBTB16 and confer cisplatin resistance, alongside HSP90- and USP38-mediated protection from degradation.","evidence":"Co-IP, ubiquitination assays, ChIP, shRNA, in vivo xenograft","pmids":["38287116","29989047"],"confidence":"Medium","gaps":["Single-lab target links","Generalizability of USP7-KDM5B axis beyond nasopharyngeal carcinoma untested"]},{"year":null,"claim":"How KDM5B's catalytic versus scaffolding modes are selected at individual loci, and how its many post-translational modifiers and partner complexes are coordinated in a given cell state, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model integrating reader domains, partner complexes, and PTMs for context-specific targeting","Structure of KDM5B engaged with a full repressive complex on nucleosomes lacking","Determinants distinguishing repressed vs. activated outcomes per locus undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,1,5,16,18,34]},{"term_id":"GO:0016491","term_label":"oxidoreductase activity","supporting_discovery_ids":[0,1,17,18]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[6]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[9,13]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[4,5,16]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[19,38]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[39]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[5,12,13,39]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[11,14]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,5,11,13]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[5,16,22]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[14,29]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[19,26,30,35]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[12,25,33,34]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[15,16,23]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[24,31,32]}],"complexes":["LSD1/NuRD complex","PRC2 (via SUZ12)"],"partners":["LSD1","HDAC1","MRG15","SUZ12","SETDB1","AR","ESR1","TFAP2C"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UGL1","full_name":"Lysine-specific demethylase 5B","aliases":["Cancer/testis antigen 31","CT31","Histone demethylase JARID1B","Jumonji/ARID domain-containing protein 1B","PLU-1","Retinoblastoma-binding protein 2 homolog 1","RBP2-H1","[histone H3]-trimethyl-L-lysine(4) demethylase 5B"],"length_aa":1544,"mass_kda":175.7,"function":"Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code (PubMed:24952722, PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5 (PubMed:24952722). In contrast, may act as a tumor suppressor for melanoma. Represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9UGL1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KDM5B","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGN5","stoichiometry":0.2},{"gene":"NUCKS1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KDM5B","total_profiled":1310},"omim":[{"mim_id":"618109","title":"INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 65; MRT65","url":"https://www.omim.org/entry/618109"},{"mim_id":"609132","title":"LYSINE DEMETHYLASE 1A; KDM1A","url":"https://www.omim.org/entry/609132"},{"mim_id":"606834","title":"LYSINE-SPECIFIC METHYLTRANSFERASE 2B; KMT2B","url":"https://www.omim.org/entry/606834"},{"mim_id":"605393","title":"LYSINE DEMETHYLASE 5B; KDM5B","url":"https://www.omim.org/entry/605393"},{"mim_id":"604782","title":"ASH2-LIKE; ASH2L","url":"https://www.omim.org/entry/604782"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":34.5}],"url":"https://www.proteinatlas.org/search/KDM5B"},"hgnc":{"alias_symbol":["RBBP2H1A","PLU-1","CT31","PPP1R98"],"prev_symbol":["JARID1B"]},"alphafold":{"accession":"Q9UGL1","domains":[{"cath_id":"2.60.120.650","chopping":"37-90_374-604","consensus_level":"high","plddt":87.6362,"start":37,"end":604},{"cath_id":"1.10.150.60","chopping":"102-216_312-363","consensus_level":"medium","plddt":72.6892,"start":102,"end":363},{"cath_id":"-","chopping":"606-756","consensus_level":"medium","plddt":92.1519,"start":606,"end":756},{"cath_id":"-","chopping":"930-1047","consensus_level":"medium","plddt":87.8866,"start":930,"end":1047},{"cath_id":"-","chopping":"1055-1096_1130-1166_1178-1275_1339-1368","consensus_level":"medium","plddt":83.0188,"start":1055,"end":1368},{"cath_id":"3.30.40.10","chopping":"1491-1544","consensus_level":"medium","plddt":78.3257,"start":1491,"end":1544}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UGL1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UGL1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UGL1-F1-predicted_aligned_error_v6.png","plddt_mean":72.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KDM5B","jax_strain_url":"https://www.jax.org/strain/search?query=KDM5B"},"sequence":{"accession":"Q9UGL1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UGL1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UGL1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UGL1"}},"corpus_meta":[{"pmid":"17363312","id":"PMC_17363312","title":"PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation.","date":"2007","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/17363312","citation_count":391,"is_preprint":false},{"pmid":"18048344","id":"PMC_18048344","title":"JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer.","date":"2007","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/18048344","citation_count":308,"is_preprint":false},{"pmid":"20832725","id":"PMC_20832725","title":"PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway.","date":"2010","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/20832725","citation_count":272,"is_preprint":false},{"pmid":"34671158","id":"PMC_34671158","title":"KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34671158","citation_count":222,"is_preprint":false},{"pmid":"10336460","id":"PMC_10336460","title":"A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10336460","citation_count":197,"is_preprint":false},{"pmid":"24937458","id":"PMC_24937458","title":"JARID1B is a luminal lineage-driving oncogene in breast cancer.","date":"2014","source":"Cancer cell","url":"https://pubmed.ncbi.nlm.nih.gov/24937458","citation_count":163,"is_preprint":false},{"pmid":"22020125","id":"PMC_22020125","title":"Jarid1b targets genes regulating development and is involved in neural differentiation.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/22020125","citation_count":162,"is_preprint":false},{"pmid":"27214403","id":"PMC_27214403","title":"Structural analysis of human KDM5B guides histone demethylase inhibitor development.","date":"2016","source":"Nature chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/27214403","citation_count":157,"is_preprint":false},{"pmid":"21937684","id":"PMC_21937684","title":"Binding of the JmjC demethylase JARID1B to LSD1/NuRD suppresses angiogenesis and metastasis in breast cancer cells by repressing chemokine CCL14.","date":"2011","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/21937684","citation_count":152,"is_preprint":false},{"pmid":"24412361","id":"PMC_24412361","title":"The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers.","date":"2014","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/24412361","citation_count":140,"is_preprint":false},{"pmid":"21448134","id":"PMC_21448134","title":"KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21448134","citation_count":137,"is_preprint":false},{"pmid":"21369698","id":"PMC_21369698","title":"PLU-1/JARID1B/KDM5B is required for embryonic survival and contributes to cell proliferation in the mammary gland and in ER+ breast cancer cells.","date":"2011","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/21369698","citation_count":131,"is_preprint":false},{"pmid":"22615382","id":"PMC_22615382","title":"H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.","date":"2012","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/22615382","citation_count":126,"is_preprint":false},{"pmid":"24778210","id":"PMC_24778210","title":"Histone demethylase KDM5B is a key regulator of genome stability.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24778210","citation_count":121,"is_preprint":false},{"pmid":"12237901","id":"PMC_12237901","title":"PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen?","date":"2002","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/12237901","citation_count":117,"is_preprint":false},{"pmid":"24495580","id":"PMC_24495580","title":"KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation.","date":"2014","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/24495580","citation_count":117,"is_preprint":false},{"pmid":"17709396","id":"PMC_17709396","title":"Functional analysis of the transcription repressor PLU-1/JARID1B.","date":"2007","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17709396","citation_count":106,"is_preprint":false},{"pmid":"23637629","id":"PMC_23637629","title":"The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.","date":"2013","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23637629","citation_count":105,"is_preprint":false},{"pmid":"26917489","id":"PMC_26917489","title":"Aberrant KDM5B expression promotes aggressive breast cancer through MALAT1 overexpression and downregulation of hsa-miR-448.","date":"2016","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/26917489","citation_count":103,"is_preprint":false},{"pmid":"18591252","id":"PMC_18591252","title":"The histone demethylase KDM5b/JARID1b plays a role in cell fate decisions by blocking terminal differentiation.","date":"2008","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/18591252","citation_count":99,"is_preprint":false},{"pmid":"30448242","id":"PMC_30448242","title":"KDM5B is a master regulator of the H3K4-methylome in stem cells, development and cancer.","date":"2018","source":"Seminars in cancer biology","url":"https://pubmed.ncbi.nlm.nih.gov/30448242","citation_count":94,"is_preprint":false},{"pmid":"17373667","id":"PMC_17373667","title":"Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases.","date":"2007","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/17373667","citation_count":81,"is_preprint":false},{"pmid":"12657635","id":"PMC_12657635","title":"Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12657635","citation_count":80,"is_preprint":false},{"pmid":"21969366","id":"PMC_21969366","title":"Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression through epigenetic repression of microRNA let-7e.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21969366","citation_count":79,"is_preprint":false},{"pmid":"30978340","id":"PMC_30978340","title":"KDM5B promotes breast cancer cell proliferation and migration via AMPK-mediated lipid metabolism reprogramming.","date":"2019","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/30978340","citation_count":76,"is_preprint":false},{"pmid":"26083387","id":"PMC_26083387","title":"RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis In Vivo.","date":"2015","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/26083387","citation_count":71,"is_preprint":false},{"pmid":"25909289","id":"PMC_25909289","title":"JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells.","date":"2015","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/25909289","citation_count":68,"is_preprint":false},{"pmid":"26453309","id":"PMC_26453309","title":"Epigenetic Control of the Bone-master Runx2 Gene during Osteoblast-lineage Commitment by the Histone Demethylase JARID1B/KDM5B.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26453309","citation_count":68,"is_preprint":false},{"pmid":"22371483","id":"PMC_22371483","title":"Histone demethylase KDM5B collaborates with TFAP2C and Myc to repress the cell cycle inhibitor p21(cip) (CDKN1A).","date":"2012","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22371483","citation_count":68,"is_preprint":false},{"pmid":"17973255","id":"PMC_17973255","title":"RBP2-H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells.","date":"2008","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/17973255","citation_count":66,"is_preprint":false},{"pmid":"22420752","id":"PMC_22420752","title":"Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor.","date":"2012","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/22420752","citation_count":64,"is_preprint":false},{"pmid":"28082020","id":"PMC_28082020","title":"miR424-5p functions as an anti-oncogene in cervical cancer cell growth by targeting KDM5B via the Notch signaling pathway.","date":"2017","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/28082020","citation_count":63,"is_preprint":false},{"pmid":"22152480","id":"PMC_22152480","title":"FOXP3 orchestrates H4K16 acetylation and H3K4 trimethylation for activation of multiple genes by recruiting MOF and causing displacement of PLU-1.","date":"2011","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/22152480","citation_count":62,"is_preprint":false},{"pmid":"24100015","id":"PMC_24100015","title":"Extended self-renewal and accelerated reprogramming in the absence of Kdm5b.","date":"2013","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/24100015","citation_count":60,"is_preprint":false},{"pmid":"23777767","id":"PMC_23777767","title":"RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity.","date":"2013","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/23777767","citation_count":58,"is_preprint":false},{"pmid":"25628922","id":"PMC_25628922","title":"KDM5B is overexpressed in gastric cancer and is required for gastric cancer cell proliferation and metastasis.","date":"2014","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/25628922","citation_count":56,"is_preprint":false},{"pmid":"29989047","id":"PMC_29989047","title":"KDM5B demethylates H3K4 to recruit XRCC1 and promote chemoresistance.","date":"2018","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29989047","citation_count":55,"is_preprint":false},{"pmid":"26184998","id":"PMC_26184998","title":"Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma.","date":"2015","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/26184998","citation_count":54,"is_preprint":false},{"pmid":"29934325","id":"PMC_29934325","title":"Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1.","date":"2018","source":"Molecular cancer research : MCR","url":"https://pubmed.ncbi.nlm.nih.gov/29934325","citation_count":54,"is_preprint":false},{"pmid":"25951238","id":"PMC_25951238","title":"JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25951238","citation_count":52,"is_preprint":false},{"pmid":"33240782","id":"PMC_33240782","title":"USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation.","date":"2020","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/33240782","citation_count":52,"is_preprint":false},{"pmid":"23354547","id":"PMC_23354547","title":"Depletion of JARID1B induces cellular senescence in human colorectal cancer.","date":"2013","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/23354547","citation_count":50,"is_preprint":false},{"pmid":"26655717","id":"PMC_26655717","title":"Transcriptional Regulation of JARID1B/KDM5B Histone Demethylase by Ikaros, Histone Deacetylase 1 (HDAC1), and Casein Kinase 2 (CK2) in B-cell Acute Lymphoblastic Leukemia.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26655717","citation_count":49,"is_preprint":false},{"pmid":"25596733","id":"PMC_25596733","title":"SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination.","date":"2015","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/25596733","citation_count":48,"is_preprint":false},{"pmid":"20863814","id":"PMC_20863814","title":"Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10.","date":"2010","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/20863814","citation_count":48,"is_preprint":false},{"pmid":"30523048","id":"PMC_30523048","title":"KDM5B Promotes Drug Resistance by Regulating Melanoma-Propagating Cell Subpopulations.","date":"2018","source":"Molecular cancer therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/30523048","citation_count":47,"is_preprint":false},{"pmid":"23907094","id":"PMC_23907094","title":"Androgen receptor activation by polychlorinated biphenyls: epigenetic effects mediated by the histone demethylase Jarid1b.","date":"2013","source":"Epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/23907094","citation_count":47,"is_preprint":false},{"pmid":"27488530","id":"PMC_27488530","title":"JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers.","date":"2016","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/27488530","citation_count":46,"is_preprint":false},{"pmid":"24802759","id":"PMC_24802759","title":"Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24802759","citation_count":45,"is_preprint":false},{"pmid":"25450384","id":"PMC_25450384","title":"Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21.","date":"2014","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/25450384","citation_count":45,"is_preprint":false},{"pmid":"32868382","id":"PMC_32868382","title":"KDM5B Is Essential for the Hyperactivation of PI3K/AKT Signaling in Prostate Tumorigenesis.","date":"2020","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/32868382","citation_count":43,"is_preprint":false},{"pmid":"38287116","id":"PMC_38287116","title":"Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.","date":"2024","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/38287116","citation_count":42,"is_preprint":false},{"pmid":"30343192","id":"PMC_30343192","title":"Lysine demethylase 5B (KDM5B): A potential anti-cancer drug target.","date":"2018","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30343192","citation_count":42,"is_preprint":false},{"pmid":"26131109","id":"PMC_26131109","title":"MiR-29a suppresses prostate cell proliferation and induces apoptosis via KDM5B protein regulation.","date":"2015","source":"International journal of clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26131109","citation_count":42,"is_preprint":false},{"pmid":"21980403","id":"PMC_21980403","title":"The histone demethylase Jarid1b (Kdm5b) is a novel component of the Rb pathway and associates with E2f-target genes in MEFs during senescence.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21980403","citation_count":41,"is_preprint":false},{"pmid":"32751840","id":"PMC_32751840","title":"Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy.","date":"2020","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/32751840","citation_count":39,"is_preprint":false},{"pmid":"36914768","id":"PMC_36914768","title":"Histone demethylase KDM5B licenses macrophage-mediated inflammatory responses by repressing Nfkbia transcription.","date":"2023","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/36914768","citation_count":38,"is_preprint":false},{"pmid":"30728054","id":"PMC_30728054","title":"SNHG1 promotes malignant biological behaviors of glioma cells via microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B participating positive feedback loop.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/30728054","citation_count":37,"is_preprint":false},{"pmid":"33829656","id":"PMC_33829656","title":"KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis.","date":"2021","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33829656","citation_count":35,"is_preprint":false},{"pmid":"36481938","id":"PMC_36481938","title":"Loss of KDM5B ameliorates pathological cardiac fibrosis and dysfunction by epigenetically enhancing ATF3 expression.","date":"2022","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36481938","citation_count":34,"is_preprint":false},{"pmid":"25655602","id":"PMC_25655602","title":"The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice.","date":"2015","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/25655602","citation_count":34,"is_preprint":false},{"pmid":"29602065","id":"PMC_29602065","title":"Targeting histone demethylases KDM5A and KDM5B in AML cancer cells: A comparative view.","date":"2018","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/29602065","citation_count":34,"is_preprint":false},{"pmid":"35217626","id":"PMC_35217626","title":"A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia.","date":"2022","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/35217626","citation_count":33,"is_preprint":false},{"pmid":"27874950","id":"PMC_27874950","title":"miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting KDM5B.","date":"2016","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/27874950","citation_count":33,"is_preprint":false},{"pmid":"14579128","id":"PMC_14579128","title":"PLU-1, a transcriptional repressor and putative testis-cancer antigen, has a specific expression and localisation pattern during meiosis.","date":"2003","source":"Chromosoma","url":"https://pubmed.ncbi.nlm.nih.gov/14579128","citation_count":32,"is_preprint":false},{"pmid":"26023081","id":"PMC_26023081","title":"Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5.","date":"2015","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/26023081","citation_count":32,"is_preprint":false},{"pmid":"31229500","id":"PMC_31229500","title":"Targeting the H3K4 Demethylase KDM5B Reprograms the Metabolome and Phenotype of Melanoma Cells.","date":"2019","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/31229500","citation_count":31,"is_preprint":false},{"pmid":"25877751","id":"PMC_25877751","title":"JARID1B modulates lung cancer cell proliferation and invasion by regulating p53 expression.","date":"2015","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25877751","citation_count":30,"is_preprint":false},{"pmid":"30588710","id":"PMC_30588710","title":"JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer.","date":"2019","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/30588710","citation_count":30,"is_preprint":false},{"pmid":"24649241","id":"PMC_24649241","title":"Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth.","date":"2013","source":"Molecular and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/24649241","citation_count":30,"is_preprint":false},{"pmid":"32155529","id":"PMC_32155529","title":"Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B).","date":"2020","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32155529","citation_count":29,"is_preprint":false},{"pmid":"35428764","id":"PMC_35428764","title":"KDM5B promotes tumorigenesis of Ewing sarcoma via FBXW7/CCNE1 axis.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/35428764","citation_count":28,"is_preprint":false},{"pmid":"32211412","id":"PMC_32211412","title":"Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos.","date":"2020","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/32211412","citation_count":27,"is_preprint":false},{"pmid":"31060229","id":"PMC_31060229","title":"Small Molecule Inhibitors of KDM5 Histone Demethylases Increase the Radiosensitivity of Breast Cancer Cells Overexpressing JARID1B.","date":"2019","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31060229","citation_count":27,"is_preprint":false},{"pmid":"30658067","id":"PMC_30658067","title":"Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma.","date":"2019","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/30658067","citation_count":26,"is_preprint":false},{"pmid":"30217758","id":"PMC_30217758","title":"Novel KDM5B splice variants identified in patients with developmental disorders: Functional consequences.","date":"2018","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/30217758","citation_count":26,"is_preprint":false},{"pmid":"36509829","id":"PMC_36509829","title":"Drawing a line between histone demethylase KDM5A and KDM5B: their roles in development and tumorigenesis.","date":"2022","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36509829","citation_count":25,"is_preprint":false},{"pmid":"24619877","id":"PMC_24619877","title":"Coordinated regulation of retinoic acid signaling pathway by KDM5B and polycomb repressive complex 2.","date":"2014","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24619877","citation_count":25,"is_preprint":false},{"pmid":"31805991","id":"PMC_31805991","title":"Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells.","date":"2019","source":"Breast cancer research : BCR","url":"https://pubmed.ncbi.nlm.nih.gov/31805991","citation_count":25,"is_preprint":false},{"pmid":"33109187","id":"PMC_33109187","title":"JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level.","date":"2020","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/33109187","citation_count":24,"is_preprint":false},{"pmid":"31467927","id":"PMC_31467927","title":"The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis.","date":"2019","source":"Journal of diabetes research","url":"https://pubmed.ncbi.nlm.nih.gov/31467927","citation_count":24,"is_preprint":false},{"pmid":"28566884","id":"PMC_28566884","title":"Hepatitis B virus X protein induces hepatic stem cell-like features in hepatocellular carcinoma by activating KDM5B.","date":"2017","source":"World journal of gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/28566884","citation_count":24,"is_preprint":false},{"pmid":"26739753","id":"PMC_26739753","title":"Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice.","date":"2016","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/26739753","citation_count":23,"is_preprint":false},{"pmid":"31776402","id":"PMC_31776402","title":"Phosphorylation of the histone demethylase KDM5B and regulation of the phenotype of triple negative breast cancer.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31776402","citation_count":21,"is_preprint":false},{"pmid":"36112701","id":"PMC_36112701","title":"Discovery of Novel Pyrazole-Based KDM5B Inhibitor TK-129 and Its Protective Effects on Myocardial Remodeling and Fibrosis.","date":"2022","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/36112701","citation_count":21,"is_preprint":false},{"pmid":"27480251","id":"PMC_27480251","title":"Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells.","date":"2016","source":"Experimental biology and medicine (Maywood, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/27480251","citation_count":21,"is_preprint":false},{"pmid":"26125737","id":"PMC_26125737","title":"Immunohistochemical detection and clinicopathological significance of JARID1B/KDM5B and P16 expression in invasive ductal carcinoma of the breast.","date":"2015","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/26125737","citation_count":20,"is_preprint":false},{"pmid":"12617814","id":"PMC_12617814","title":"Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer.","date":"2002","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/12617814","citation_count":19,"is_preprint":false},{"pmid":"37152294","id":"PMC_37152294","title":"The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer.","date":"2023","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/37152294","citation_count":19,"is_preprint":false},{"pmid":"27584795","id":"PMC_27584795","title":"Overexpression of JARID1B promotes differentiation via SHIP1/AKT signaling in human hypopharyngeal squamous cell carcinoma.","date":"2016","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/27584795","citation_count":19,"is_preprint":false},{"pmid":"23262439","id":"PMC_23262439","title":"JARID1B expression in human melanoma and benign melanocytic skin lesions.","date":"2013","source":"Melanoma research","url":"https://pubmed.ncbi.nlm.nih.gov/23262439","citation_count":19,"is_preprint":false},{"pmid":"23579952","id":"PMC_23579952","title":"Connexin 26 is down-regulated by KDM5B in the progression of bladder cancer.","date":"2013","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/23579952","citation_count":19,"is_preprint":false},{"pmid":"40059116","id":"PMC_40059116","title":"Epstein-Barr virus hijacks histone demethylase machinery to drive epithelial malignancy progression through KDM5B upregulation.","date":"2025","source":"Signal transduction and targeted therapy","url":"https://pubmed.ncbi.nlm.nih.gov/40059116","citation_count":17,"is_preprint":false},{"pmid":"14516692","id":"PMC_14516692","title":"Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer.","date":"2002","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/14516692","citation_count":17,"is_preprint":false},{"pmid":"32007477","id":"PMC_32007477","title":"Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions.","date":"2020","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/32007477","citation_count":17,"is_preprint":false},{"pmid":"34522457","id":"PMC_34522457","title":"MiR-374b-5p inhibits KDM5B-induced epithelial-mesenchymal transition in pancreatic cancer.","date":"2021","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/34522457","citation_count":17,"is_preprint":false},{"pmid":"35468265","id":"PMC_35468265","title":"Alcohol-associated fibrosis in females is mediated by female-specific activation of lysine demethylases KDM5B and KDM5C.","date":"2022","source":"Hepatology communications","url":"https://pubmed.ncbi.nlm.nih.gov/35468265","citation_count":17,"is_preprint":false},{"pmid":"35440714","id":"PMC_35440714","title":"H3K4 demethylase KDM5B regulates cancer cell identity and epigenetic plasticity.","date":"2022","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/35440714","citation_count":16,"is_preprint":false},{"pmid":"35946516","id":"PMC_35946516","title":"KDM5B regulates the PTEN/PI3K/Akt pathway to increase sorafenib-resistance in hepatocellular carcinoma.","date":"2022","source":"Anti-cancer drugs","url":"https://pubmed.ncbi.nlm.nih.gov/35946516","citation_count":16,"is_preprint":false},{"pmid":"37137887","id":"PMC_37137887","title":"Downregulated liver-elevated long intergenic noncoding RNA (LINC02428) is a tumor suppressor that blocks KDM5B/IGF2BP1 positive feedback loop in hepatocellular carcinoma.","date":"2023","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/37137887","citation_count":16,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":50629,"output_tokens":9495,"usd":0.147156,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":19503,"output_tokens":5112,"usd":0.112657,"stage2_stop_reason":"end_turn"},"total_usd":0.259813,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"PLU-1/KDM5B is a histone demethylase that directly removes the trimethyl mark from H3K4 (H3K4me3), demonstrated by in vitro biochemical demethylation assays and active-site mutagenesis of the JmjC domain.\",\n      \"method\": \"In vitro histone demethylation assay, JmjC domain mutagenesis, mass spectrometry\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with mutagenesis confirmed in two independent 2007 papers (PMID:17363312 and PMID:18048344), replicated across labs\",\n      \"pmids\": [\"17363312\", \"18048344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KDM5B demethylase activity requires the JmjC domain and uses Fe(II) and alpha-ketoglutarate as cofactors, classifying it as a 2-oxoglutarate-dependent dioxygenase.\",\n      \"method\": \"In vitro biochemical assay with cofactor supplementation and chelation; JmjC domain mutagenesis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro biochemical reconstitution with cofactor dependency confirmed; replicated across multiple papers\",\n      \"pmids\": [\"18048344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KDM5B associates with the androgen receptor (AR) and regulates its transcriptional activity, demonstrated by co-immunoprecipitation and reporter assays.\",\n      \"method\": \"Co-immunoprecipitation, transcriptional reporter assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP plus reporter assay, single lab, replicated in a separate study (PMID:23907094)\",\n      \"pmids\": [\"18048344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PARP-1 inhibits KDM5B demethylase activity by PARylating KDM5B and excluding it from promoters, thereby protecting H3K4me3 marks and maintaining a permissive chromatin environment for transcription.\",\n      \"method\": \"ChIP, RNAi knockdown, PARylation assay, promoter occupancy analysis\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal ChIP and functional RNAi with defined molecular outcomes, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"20832725\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"KDM5B (PLU-1) interacts directly with developmental transcription factors BF-1 and PAX9 via a conserved VP motif in those proteins; this interaction requires specific residues in the VP motif (demonstrated by site-directed mutagenesis) and enhances transcriptional repression.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis, reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid confirmed by co-IP and mutagenesis, single lab with multiple methods\",\n      \"pmids\": [\"12657635\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KDM5B directly represses target genes including BRCA1 and metallothionein genes (MT1H, MT1F, MT1X) by binding their promoters and reducing H3K4me3 levels, demonstrated by ChIP and siRNA knockdown with microarray analysis.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), microarray, RNAi knockdown, overexpression\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ChIP confirmed direct promoter binding, H3K4me3 changes measured, and microarray used to identify targets; replicated across multiple studies\",\n      \"pmids\": [\"17709396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KDM5B binds CG-rich DNA through its ARID domain, with the GCACA/C motif identified as a consensus binding sequence.\",\n      \"method\": \"EMSA, mutagenesis, reporter assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — DNA binding demonstrated biochemically with motif identification by mutagenesis, single lab\",\n      \"pmids\": [\"17709396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KDM5B directly interacts with class I and class IIa histone deacetylases (HDACs), with two PHD domains of KDM5B binding a domain in the 5' region of HDAC4 overlapping the MEF-2 binding region.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, co-localization in MAD bodies upon co-transfection\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding demonstrated with domain mapping and co-IP, single lab with two methods\",\n      \"pmids\": [\"17373667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"KDM5B is a physical component of the LSD1/NuRD complex; KDM5B and LSD1 act sequentially and coordinately to demethylate H3K4, repressing the CCL14 chemokine pathway to suppress angiogenesis and metastasis in breast cancer.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, genome-wide transcriptional analysis, in vivo xenograft\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complex membership confirmed by Co-IP, ChIP confirms promoter occupancy, functional in vivo validation; multiple orthogonal methods\",\n      \"pmids\": [\"21937684\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KDM5B PHD1 finger binds unmodified histone H3 (H3K4me0) with high specificity, whereas PHD3 finger preferentially binds H3K4me3; PHD1-H3K4me0 interaction is essential for KDM5B's role in inhibiting cell migration.\",\n      \"method\": \"Peptide pulldown, histone binding assays, domain mutagenesis, RNA-seq, migration assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro histone binding reconstitution with domain mutagenesis and functional validation in cell migration assay; multiple orthogonal methods\",\n      \"pmids\": [\"24412361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KDM5B associates with components of the NuRD complex (including HDAC1) and cooperates with HDAC1 for gene repression, demonstrated by biochemical co-immunoprecipitation.\",\n      \"method\": \"Co-immunoprecipitation\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP, consistent with prior NuRD complex evidence from other studies\",\n      \"pmids\": [\"24412361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"KDM5B is recruited to intragenic regions via interaction with the chromodomain protein MRG15, which recognizes H3K36me3; KDM5B depletion leads to increased intragenic H3K4me3 and cryptic intragenic transcription, impairing transcriptional elongation of self-renewal genes.\",\n      \"method\": \"ChIP-seq, Co-immunoprecipitation, RNAi knockdown with RNA-seq, H3K36me3 interaction assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal ChIP-seq and Co-IP with defined functional consequences, multiple orthogonal methods in one study\",\n      \"pmids\": [\"21448134\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Jarid1b/KDM5B localizes predominantly to transcription start sites of developmental regulator genes; its depletion leads to global increases in H3K4me3 and failure to silence lineage-inappropriate genes during ESC neural differentiation.\",\n      \"method\": \"Genome-wide ChIP-seq (location analysis), RNAi knockdown, differentiation assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide ChIP-seq with functional KD and differentiation readout; replicated in multiple ESC papers\",\n      \"pmids\": [\"22020125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KDM5B co-localizes with H3K4me3 at promoters and enhancers of active genes; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, linking KDM5B to focusing of H3K4 methylation.\",\n      \"method\": \"ChIP-seq, RNAi knockdown\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq with KD phenotype, multiple functional outcomes, single lab\",\n      \"pmids\": [\"24495580\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KDM5B becomes enriched at DNA double-strand break (DSB) sites in a PARP1- and macroH2A1.1-dependent manner, and is required for efficient DSB repair and for recruitment of Ku70 and BRCA1 to damage sites.\",\n      \"method\": \"Laser micro-irradiation, immunofluorescence, RNAi knockdown, γH2AX foci, clonogenic survival\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization to damage sites with functional readout (recruitment of Ku70/BRCA1), multiple methods in one study\",\n      \"pmids\": [\"24778210\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Jarid1b/KDM5B is a component of the Rb pathway: depletion of Jarid1b phenocopies Rb1 knockdown, and Jarid1b associates with E2F-target gene promoters during senescence to mediate H3K4 demethylation-dependent gene silencing.\",\n      \"method\": \"Functional genetic screen for senescence bypass, RNAi, ChIP, E2F-target promoter analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis by genetic screen plus ChIP, single lab with two orthogonal methods\",\n      \"pmids\": [\"22615382\", \"21980403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"KDM5B forms a ternary complex with TFAP2C and Myc at the CDKN1A proximal promoter; all three factors collaborate for optimal CDKN1A repression, which requires the AP-2 binding site at -111/-103 and KDM5B demethylase activity.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, luciferase reporter assay, domain mapping, demethylase-dead mutant\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP confirmed ternary complex, ChIP confirmed promoter occupancy, demethylase-dead mutant validates catalytic requirement; multiple orthogonal methods\",\n      \"pmids\": [\"22371483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structures of the catalytic core of human KDM5B in complex with three distinct inhibitor chemotypes revealed the 2-oxoglutarate binding site geometry and selectivity determinants; KDM5B active site shares hybrid features with KDM4 and KDM6 families.\",\n      \"method\": \"X-ray crystallography, in vitro enzymatic inhibition assays, cellular H3K4me3 elevation\",\n      \"journal\": \"Nature chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structures with functional validation by inhibitor biochemistry and cellular assay; single lab but multiple co-crystal structures\",\n      \"pmids\": [\"27214403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Recombinant KDM5B catalytic core demethylates H3K4me3 and H3K4me2 in vitro with an apparent Km of 0.5 µM for H3K4me3 peptide substrate; 2,4-pyridinedicarboxylic acid (2,4-PDCA) inhibits KDM5B both in vitro and in cells.\",\n      \"method\": \"In vitro enzymatic assay with recombinant protein, kinetic characterization, cell-based inhibitor assay\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — purified recombinant enzyme with Michaelis-Menten kinetics, in vitro and cellular inhibitor validation\",\n      \"pmids\": [\"22420752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KDM5B recruits the H3K9 methyltransferase SETDB1 to silence endogenous retroelements in a demethylase-independent manner; derepression of retroelements activates cytosolic RNA/DNA sensing and type-I interferon responses leading to tumor rejection.\",\n      \"method\": \"RNAi knockdown, Co-immunoprecipitation (KDM5B-SETDB1), MMVL30 retroelement de-repression assay, innate immune reporter assays, mouse melanoma models\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP of KDM5B-SETDB1, functional in vivo mouse melanoma models with defined immune phenotype, demethylase-independence established by catalytic mutant\",\n      \"pmids\": [\"34671158\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"KDM5B acts as a corepressor for the transcription factor TIEG1/KLF10; the repression domains of TIEG1 bind the C-terminus of KDM5B, and KDM5B knockdown increases Smad7 mRNA levels, linking KDM5B to TGF-β signaling repression.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, RNAi knockdown, RT-PCR\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP with domain mapping and functional RNAi knockdown, single lab\",\n      \"pmids\": [\"20863814\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"FOXP3 activates target genes by recruiting MOF (histone acetyltransferase) and simultaneously displacing KDM5B (PLU-1) from promoters, increasing both H4K16 acetylation and H3K4me3.\",\n      \"method\": \"ChIP, RNAi, reporter assay, Co-immunoprecipitation\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms displacement of KDM5B upon FOXP3 recruitment; RNAi validates functional consequence; single lab with two methods\",\n      \"pmids\": [\"22152480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KDM5B associates with PRC2 via direct interaction between KDM5B and the SUZ12 component; co-occupancy at RA-responsive genes leads to a biphasic regulatory effect on retinoic acid signaling through decoupled H3K4me3 demethylation and PRC2-antagonizing activities.\",\n      \"method\": \"Co-immunoprecipitation, in vitro pulldown, ChIP, reporter assay\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct pulldown confirms SUZ12 interaction, ChIP and reporter assays, single lab\",\n      \"pmids\": [\"24619877\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"JARID1B epigenetically represses the tumor suppressor microRNA let-7e by binding to its promoter region and removing the H3K4me3 mark, leading to cyclin D1 upregulation and G1-to-S cell cycle progression in breast cancer cells.\",\n      \"method\": \"ChIP, RNAi, cell cycle analysis, luciferase reporter, RT-PCR\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms promoter binding with H3K4me3 reduction, rescue experiment with let-7e inhibitor, single lab\",\n      \"pmids\": [\"21969366\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"KDM5B represses H3K4me3 at the PTEN promoter, reducing PTEN transcription and thereby activating the downstream PI3K/AKT pathway to promote hepatocellular carcinoma metastasis.\",\n      \"method\": \"ChIP, overexpression, RNAi knockdown, rescue with PTEN overexpression, in vivo xenograft\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms direct promoter binding with H3K4me3 reduction, pathway rescue experiment, single lab\",\n      \"pmids\": [\"25909289\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"KDM5B represses expression of H3K4me2/3 at the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells; KDM5B knockdown (but not UTX or NO66 knockdown) prevents repression of this promoter, identifying KDM5B as a specific component of the epigenetic switch controlling osteoblast vs. myoblast lineage commitment.\",\n      \"method\": \"RNAi knockdown, ChIP, differentiation assays, epistasis (UTX/NO66 controls)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and specific knockdown epistasis with paralog controls, single lab\",\n      \"pmids\": [\"26453309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"USP38 deubiquitinase couples histone ubiquitination to H3K4 demethylation by interacting with KDM5B: USP38 removes monoubiquitin from H2BK120, enabling KDM5B recruitment to promoters of proinflammatory cytokine genes (Il6, Il23a); additionally, USP38 physically binds KDM5B and prevents its proteasomal degradation.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, RNAi, ubiquitination assay, mouse endotoxin shock model\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP of USP38-KDM5B complex, ChIP confirms promoter recruitment, ubiquitination assay, in vivo validation; multiple orthogonal methods\",\n      \"pmids\": [\"33240782\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"SKP2 modulates JARID1B ubiquitination: TRAF6-mediated K63-linked ubiquitination reduces KDM5B demethylase activity and increases H3K4me3; SKP2 antagonizes TRAF6-mediated ubiquitination, thereby increasing KDM5B demethylase activity.\",\n      \"method\": \"Co-immunoprecipitation, in vivo ubiquitination assay, mouse knockout models, mass spectrometry\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ubiquitination assay with pathway epistasis, mouse model validation, single lab\",\n      \"pmids\": [\"25596733\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KDM5B is phosphorylated at Ser1456 by CDK1; this phosphorylation attenuates KDM5B occupancy on promoters of pluripotency genes (SOX2, NANOG), reducing their repression and modulating stem cell population in triple-negative breast cancer.\",\n      \"method\": \"Mass spectrometry phosphorylation mapping, ChIP, CDK1 kinase assay, RNAi, stem cell marker analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-identified site validated with CDK1 kinase assay and ChIP occupancy changes, single lab\",\n      \"pmids\": [\"31776402\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KDM5B demethylates H3K4 at the XRCC1 locus to facilitate XRCC1 recruitment to DNA damage sites, and HSP90 protects KDM5B from ubiquitin-dependent proteasomal degradation by forming a complex with it.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, ChIP, γH2AX co-localization, knockdown, HSP90 inhibitor degradation assay\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and MS identify HSP90-KDM5B complex, ChIP links H3K4 demethylation to XRCC1 recruitment, single lab\",\n      \"pmids\": [\"29989047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In activated macrophages, KDM5B is selectively recruited to the Nfkbia (IκBα) promoter where it erases H3K4me3 and decreases chromatin accessibility, thereby suppressing IκBα expression and enabling full NF-κB activation and pro-inflammatory cytokine production.\",\n      \"method\": \"Genome-wide ChIP-seq, ATAC-seq, RNAi knockdown, mouse arthritis and endotoxin models\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq identifies Nfkbia as direct target, chromatin accessibility assay, in vivo validation in two mouse models; multiple orthogonal methods\",\n      \"pmids\": [\"36914768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KDM5B directly binds the PIK3CA promoter and its loss results in reduced P110α and PIP3 levels; KDM5B controls PI3K/AKT hyperactivation in prostate cancer, demonstrated in Pten/Kdm5b double-mutant mouse models.\",\n      \"method\": \"ChIP, prostate-specific conditional knockout mouse model, western blot for PI3K pathway components, in vitro knockdown/overexpression\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms direct promoter binding, in vivo mouse epistasis model, pathway component quantification; multiple orthogonal methods\",\n      \"pmids\": [\"32868382\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"KDM5B binds to the Atf3 (ATF3) promoter and inhibits ATF3 expression by demethylating H3K4me2/3; loss of KDM5B de-represses ATF3, suppressing TGF-β-driven cardiac fibrosis.\",\n      \"method\": \"ChIP, RNAi knockdown, mouse myocardial infarction and pressure overload models, western blot\",\n      \"journal\": \"Experimental & molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms direct promoter occupancy with H3K4me3 changes, two in vivo mouse models, single lab\",\n      \"pmids\": [\"36481938\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KDM5B is required for GATA3 recruitment to the Foxa1 promoter to activate Foxa1 expression; loss of KDM5B reduces FOXA1 and ERα in mammary epithelial cells, impairing ductal development.\",\n      \"method\": \"ChIP for GATA3, KO mouse model, gene expression analysis, mammary phenotyping\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms GATA3 dependency on KDM5B at Foxa1 promoter, validated in KO mouse, single lab\",\n      \"pmids\": [\"24802759\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"KDM5B directly demethylates H3K4me3 at the HOXA5 promoter in endothelial cells, suppressing HOXA5 expression to maintain angiogenic capacity; endothelial-specific Jarid1b knockout attenuates retinal angiogenesis.\",\n      \"method\": \"ChIP, endothelial-specific conditional KO mouse (tamoxifen-inducible), shRNA knockdown, angiogenic sprouting assay, overexpression of catalytic-inactive mutant\",\n      \"journal\": \"Arteriosclerosis, thrombosis, and vascular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP confirms direct promoter demethylation, catalytic-dead mutant validates enzymatic requirement, in vivo endothelial-specific KO; multiple orthogonal methods\",\n      \"pmids\": [\"26023081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"KDM5B inhibits IFN-β and innate cytokine production in dendritic cells upon RSV infection; conditional deletion of Kdm5b in CD11c+ DCs results in higher IFN-γ and reduced Th2 cytokines in vivo.\",\n      \"method\": \"DC-specific conditional KO mouse (Kdm5bfl/fl-CD11c-Cre), siRNA knockdown, cytokine measurement, adoptive transfer model\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-type-specific conditional KO with defined cytokine phenotype, single lab, no direct ChIP linking KDM5B to specific promoters in this context\",\n      \"pmids\": [\"26083387\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Jarid1b/KDM5B is identified as a negative regulator of hematopoietic stem cell (HSC) activity: decreased Jarid1b levels expand HSCs in vitro while preserving lymphomyeloid differentiation potential; HSC regulators (Hoxa7, Hoxa9, Hoxa10, Hes1, Gata2) are upregulated upon Jarid1b knockdown.\",\n      \"method\": \"In vivo RNAi-based functional screen, in vitro HSC expansion assay, RNA sequencing\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo functional RNAi screen with RNA-seq readout, single lab\",\n      \"pmids\": [\"23777767\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The deubiquitinase USP7 deubiquitinates and stabilizes KDM5B protein; KDM5B then reduces H3K4me3 at the ZBTB16 promoter, repressing ZBTB16 and increasing TOP2A expression to confer cisplatin resistance in nasopharyngeal carcinoma.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, ChIP, shRNA knockdown, in vivo xenograft\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and ubiquitination assay confirm USP7-KDM5B interaction, ChIP confirms ZBTB16 promoter regulation, in vivo validation; single lab\",\n      \"pmids\": [\"38287116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In AML, Kdm5b directly binds and represses stemness gene promoters; the anti-AML effect relies on KDM5B's chromatin association/scaffold functions rather than its demethylase catalytic activity, as demonstrated using catalytic mutants.\",\n      \"method\": \"RNA-seq, ChIP-seq, CUT&RUN, catalytic mutant rescue experiments, KDM5B overexpression vs depletion in AML cells\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide profiling with catalytic mutant distinguishes scaffold from demethylase function, single lab\",\n      \"pmids\": [\"35217626\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"PLU-1/KDM5B protein is nuclear and localizes in discrete foci, demonstrated by transient transfection of MYC-tagged PLU-1 followed by immunofluorescence; subcellular fractionation confirmed chromatin association in somatic and meiotic cells.\",\n      \"method\": \"Immunofluorescence of tagged protein, biochemical cell fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunofluorescence and fractionation, replicated in later studies\",\n      \"pmids\": [\"10336460\", \"14579128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"KDM5B interacts with estrogen receptor alpha (ERα) and knockdown of KDM5B in MCF-7 cells dramatically decreases estrogen-stimulated tumor growth in vivo; KDM5B also regulates ERα target gene expression (e.g., progesterone receptor).\",\n      \"method\": \"Co-immunoprecipitation (tagged ERα and JARID1B), shRNAi knockdown, in vivo xenograft\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP with functional in vivo validation, single lab\",\n      \"pmids\": [\"21369698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"KDM5B inhibits expression of miR-448 by demethylating H3K4me3 at the miR-448 promoter, which in turn upregulates YTHDF3 and ITGA6 to promote HCC progression.\",\n      \"method\": \"ChIP, luciferase reporter (YTHDF3 3'UTR), RT-qPCR, knockdown/overexpression, in vivo xenograft\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP demonstrates direct H3K4me3 demethylation at miR-448 promoter, downstream pathway validated, single lab\",\n      \"pmids\": [\"33829656\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Jarid1b/KDM5B in mouse ESCs inhibits H3K4me3 at the Kdm5b-bound Reln (reelin) promoter; depletion of Kdm5b in adult SVZ neural stem cells increases H3K4me3 at the Reln locus, upregulates Reln expression and secretion, and enhances downstream Dab1 phosphorylation and migratory behavior.\",\n      \"method\": \"ChIP (H3K4me3 at Reln promoter), shRNA knockdown, immunofluorescence, extracellular reelin ELISA, phospho-Dab1 western blot, migration assay with reelin-blocking antibody rescue\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP at specific locus, functional rescue with blocking antibody confirms mechanism, single lab\",\n      \"pmids\": [\"26739753\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KDM5B (PLU-1/JARID1B) is a JmjC-domain-containing histone H3K4me3/me2/me1 demethylase that uses Fe(II) and 2-oxoglutarate as cofactors; it functions as a transcriptional repressor by directly binding gene promoters (via its ARID and PHD1/PHD3 domains that read unmodified H3K4 or H3K4me3, respectively) and erasing active H3K4me3 marks, while also participating in multi-subunit repressive complexes including LSD1/NuRD and interacting with HDACs, PRC2 (via SUZ12), TIEG1, AR, and ERα; additionally, KDM5B recruits SETDB1 to silence retroelements in a demethylase-independent scaffolding role, is regulated post-translationally by PARP1-mediated PARylation (exclusion from promoters), CDK1-mediated phosphorylation at Ser1456 (reduced promoter occupancy), USP7/USP38-mediated deubiquitination (stabilization), and TRAF6-mediated K63 ubiquitination (reduced activity), and plays essential roles in ESC differentiation, DNA double-strand break repair, hematopoietic stem cell self-renewal, innate immune regulation, and cancer cell identity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KDM5B (PLU-1/JARID1B) is a nuclear, chromatin-associated histone demethylase that erases active H3K4 trimethyl marks to act primarily as a transcriptional repressor across development, stem cell maintenance, DNA repair, immune regulation, and cancer [#0, #5, #39]. Its catalytic core is a JmjC-domain Fe(II)/2-oxoglutarate-dependent dioxygenase that removes H3K4me3 and H3K4me2 with high affinity, and its active-site geometry has been resolved crystallographically and exploited by selective inhibitors [#0, #1, #17, #18]. KDM5B reaches its targets through a combination of intrinsic chromatin readers and partner factors: its ARID domain binds CG-rich DNA, its PHD1 finger reads unmodified H3K4 while PHD3 reads H3K4me3, and it is directed to intragenic H3K36me3 regions via MRG15, focusing H3K4 methylation at promoters/enhancers and preventing cryptic transcription and lineage-inappropriate gene expression during ESC differentiation [#6, #9, #11, #12, #13]. It operates within multi-subunit repressive machinery, partnering with LSD1/NuRD-associated HDACs and PRC2 (via SUZ12), and serving as a corepressor for sequence-specific transcription factors including AR, ERα, TIEG1, and a TFAP2C/Myc complex at CDKN1A [#7, #8, #10, #16, #22, #2, #40, #20]. Through promoter-specific H3K4 demethylation KDM5B represses defined targets—BRCA1 and metallothioneins, PTEN and PIK3CA to tune PI3K/AKT signaling, and developmental/lineage genes such as HOXA5, Runx2, and Foxa1—linking it to cell migration, angiogenesis, senescence, and cancer cell identity [#5, #24, #31, #34, #25, #33]. Beyond catalysis, KDM5B has a demethylase-independent scaffolding role, recruiting SETDB1 to silence retroelements and restrain type-I interferon responses, and supporting anti-AML stemness repression through chromatin association rather than enzymatic activity [#19, #38]. KDM5B is recruited to DNA double-strand breaks in a PARP1/macroH2A1.1-dependent manner to enable Ku70, BRCA1, and XRCC1 recruitment, and it shapes innate immunity by erasing H3K4me3 at Nfkbia and proinflammatory cytokine loci [#14, #29, #30, #26]. Its abundance and chromatin occupancy are tuned post-translationally by PARP1 PARylation, CDK1 phosphorylation at Ser1456, TRAF6 K63-ubiquitination, and stabilization via USP7, USP38, and HSP90 [#3, #28, #27, #37, #26, #29].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Before its enzymatic role was known, KDM5B was shown to be a transcriptional corepressor recruited by developmental transcription factors, establishing it as a chromatin regulator embedded in repressive transcriptional programs.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP, and VP-motif mutagenesis with BF-1 and PAX9 plus reporter assays\",\n      \"pmids\": [\"12657635\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular activity defined at this stage\", \"VP-motif interaction surface on KDM5B not mapped\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The defining discovery established KDM5B as a JmjC-domain Fe(II)/2-oxoglutarate-dependent dioxygenase that directly demethylates H3K4me3, converting a transcription cofactor into a defined enzymatic eraser of an active chromatin mark.\",\n      \"evidence\": \"In vitro demethylation assays, cofactor dependency, JmjC active-site mutagenesis, mass spectrometry\",\n      \"pmids\": [\"17363312\", \"18048344\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide targeting rules not yet defined\", \"Did not resolve catalytic vs. non-catalytic functions\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Promoter-binding and direct target studies showed how KDM5B is targeted and what it represses, linking enzymatic H3K4me3 erasure to specific gene silencing including BRCA1 and metallothioneins, and to AR and HDAC corepressor partnerships.\",\n      \"evidence\": \"ChIP, microarray, EMSA/ARID motif mapping, co-IP with HDAC4 and AR, reporter assays\",\n      \"pmids\": [\"17709396\", \"17373667\", \"18048344\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Causality between H3K4me3 loss and repression not separated from complex effects\", \"HDAC/AR interactions from single labs\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Post-translational control of KDM5B was first established, showing that PARP1 PARylation excludes KDM5B from promoters to protect H3K4me3, and that TIEG1 recruits it for TGF-β-related repression.\",\n      \"evidence\": \"ChIP, PARylation assays, RNAi, co-IP and domain mapping, RT-PCR\",\n      \"pmids\": [\"20832725\", \"20863814\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and dynamics of PARylation in vivo unresolved\", \"TIEG1 link is Medium-confidence single lab\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Genome-scale and complex studies revealed how KDM5B is recruited and focuses H3K4 methylation, defining MRG15/H3K36me3-guided intragenic recruitment and LSD1/NuRD complex membership coupling H3K4 demethylation to repression.\",\n      \"evidence\": \"ChIP-seq, co-IP, H3K36me3 interaction assays, RNAi/RNA-seq, in vivo breast cancer xenograft\",\n      \"pmids\": [\"21448134\", \"21937684\", \"21369698\", \"22152480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contributions of intrinsic readers vs. partner-mediated recruitment not quantified\", \"ERα/FOXP3 links Medium-confidence\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"KDM5B was placed within cell-cycle/senescence control, acting in the Rb pathway at E2F targets and forming a TFAP2C/Myc ternary complex requiring its demethylase activity to repress CDKN1A.\",\n      \"evidence\": \"Senescence-bypass genetic screen, ChIP, co-IP, demethylase-dead mutant, luciferase assays\",\n      \"pmids\": [\"22615382\", \"21980403\", \"22371483\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct catalytic requirement at E2F targets not isolated\", \"Generalizability beyond CDKN1A unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Mechanistic dissection of chromatin reading and a non-transcriptional role emerged: PHD1 reads H3K4me0 and PHD3 reads H3K4me3 to control migration, KDM5B co-localizes with H3K4me3 to focus methylation, it links to PRC2 via SUZ12, and it is recruited to DNA double-strand breaks to enable repair factor loading.\",\n      \"evidence\": \"Peptide pulldowns, domain mutagenesis, ChIP-seq, in vitro SUZ12 pulldown, laser micro-irradiation, γH2AX foci, clonogenic survival\",\n      \"pmids\": [\"24412361\", \"24495580\", \"24619877\", \"24778210\", \"24802759\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How DSB recruitment integrates with promoter functions unresolved\", \"PRC2/GATA3 links Medium-confidence single labs\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"ESC/differentiation and tissue-specific roles consolidated KDM5B as a lineage gatekeeper and oncogenic node, demethylating H3K4 at developmental loci (HOXA5, Runx2, Reln) and at PTEN to drive PI3K/AKT-dependent cancer phenotypes, with additional ubiquitin-based regulation by TRAF6/SKP2.\",\n      \"evidence\": \"Conditional KO mice, ChIP, catalytic-inactive mutants, angiogenic/differentiation assays, in vivo ubiquitination assays\",\n      \"pmids\": [\"22020125\", \"26023081\", \"26453309\", \"26739753\", \"25909289\", \"25596733\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue-specific targeting determinants not unified\", \"Several cancer target links are Medium-confidence\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Structural and kinetic characterization of the catalytic core defined the 2-oxoglutarate binding site and selectivity determinants and enabled selective inhibitors, providing a chemical-biology framework for the enzyme.\",\n      \"evidence\": \"X-ray co-crystal structures with three inhibitor chemotypes, enzymatic inhibition, kinetic characterization, cellular H3K4me3 assays\",\n      \"pmids\": [\"27214403\", \"22420752\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length regulatory domain architecture not captured\", \"Structures of chromatin-bound complex absent\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A demethylase-independent scaffolding function was established, with KDM5B recruiting SETDB1 to silence retroelements and suppress type-I interferon responses, expanding its role beyond catalysis into immune evasion.\",\n      \"evidence\": \"Co-IP, retroelement de-repression, innate immune reporters, catalytic mutant, mouse melanoma models\",\n      \"pmids\": [\"34671158\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of SETDB1 recruitment domain mapping incomplete\", \"Interplay between catalytic and scaffold modes in same cell unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Innate immune and inflammatory roles were mechanistically anchored, with KDM5B erasing H3K4me3 and reducing accessibility at Nfkbia to enable NF-κB activation, and USP38-coupled recruitment to cytokine promoters, defining its pro-inflammatory chromatin function.\",\n      \"evidence\": \"ChIP-seq, ATAC-seq, RNAi, ubiquitination assays, mouse arthritis/endotoxin/RSV models\",\n      \"pmids\": [\"36914768\", \"33240782\", \"26083387\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How a repressor of IκBα coexists with cytokine-promoter recruitment context-dependently unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Deubiquitinase-mediated stabilization linked to therapy resistance was established, with USP7 stabilizing KDM5B to repress ZBTB16 and confer cisplatin resistance, alongside HSP90- and USP38-mediated protection from degradation.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, ChIP, shRNA, in vivo xenograft\",\n      \"pmids\": [\"38287116\", \"29989047\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab target links\", \"Generalizability of USP7-KDM5B axis beyond nasopharyngeal carcinoma untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KDM5B's catalytic versus scaffolding modes are selected at individual loci, and how its many post-translational modifiers and partner complexes are coordinated in a given cell state, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model integrating reader domains, partner complexes, and PTMs for context-specific targeting\", \"Structure of KDM5B engaged with a full repressive complex on nucleosomes lacking\", \"Determinants distinguishing repressed vs. activated outcomes per locus undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 1, 5, 16, 18, 34]},\n      {\"term_id\": \"GO:0016491\", \"supporting_discovery_ids\": [0, 1, 17, 18]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [9, 13]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [4, 5, 16]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [19, 38]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [39]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [5, 12, 13, 39]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [11, 14]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 5, 11, 13]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5, 16, 22]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [14, 29]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [19, 26, 30, 35]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [12, 25, 33, 34]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [15, 16, 23]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [24, 31, 32]}\n    ],\n    \"complexes\": [\n      \"LSD1/NuRD complex\",\n      \"PRC2 (via SUZ12)\"\n    ],\n    \"partners\": [\n      \"LSD1\",\n      \"HDAC1\",\n      \"MRG15\",\n      \"SUZ12\",\n      \"SETDB1\",\n      \"AR\",\n      \"ESR1\",\n      \"TFAP2C\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":8,"faith_total":8,"faith_pct":100.0}}