Affinage

KDM4B

Lysine-specific demethylase 4B · UniProt O94953

Length
1096 aa
Mass
121.9 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM4B (JMJD2B) is a Jumonji-C domain histone lysine demethylase that actively removes repressive H3K9me3/me2 (and H3K36 methylation) at pericentric heterochromatin and gene-regulatory regions to control chromatin state and transcription (PMID:16738407, PMID:21073875). Its catalytic architecture and K9/K36 selectivity were defined by a ternary crystal structure with H3K9me3 peptide and a 2,4-PDCA inhibitor (PMID:24971742). Chromocenter targeting depends on its PHD and Tudor domains and on the substrate-generating methyltransferase SUV39h, coupling its localization to the H3K9me3 mark it erases (PMID:21073875). Functionally, KDM4B acts as a transcriptional coactivator that demethylates H3K9me3 at promoters and enhancers bound by lineage and signal-responsive transcription factors, and at ERα target genes its H3K9 demethylation is a prerequisite for MLL2-mediated H3K4 methylation, enforcing mutual exclusivity of the two marks (PMID:21502505, PMID:21445275). Across cell types it partners with sequence-specific factors—ERα, AR, GATA-3, C/EBPβ, MyoD, c-Jun, c-Myc/N-Myc, NF-κB p65, β-catenin/TCF4, and TFAP2C/LSD1—to derepress target loci, driving programs from steroid-responsive growth to mesenchymal/skeletal differentiation (PMID:23723241, PMID:22722334, PMID:24481461, PMID:34031372, PMID:25925418, PMID:25534856, PMID:33441614). KDM4B is itself an induced effector node: HIF-1α, p53, and steroid receptors transcriptionally activate it (PMID:18984585, PMID:28073943, PMID:23435229), while its protein stability is set by Hsp90 binding, SCF^Fbxo22 ubiquitination, ERK phosphorylation, and UCHL1 deubiquitination (PMID:23589305, PMID:30418174, PMID:28945223, PMID:38743986). In stem and progenitor cells it sustains ESC self-renewal within the Nanog regulatory module and directs mesenchymal stem cell fate toward osteo/chondrogenesis via H3K9me3 removal at DLX and SOX9 loci (PMID:24361252, PMID:22770241, PMID:26485430, PMID:33571444). KDM4B also has non-canonical activities: PARP1-dependent recruitment to double-strand breaks promoting heterochromatin repair (PMID:23744078), a PKA-phosphorylated splicing-scaffold role coupling the spliceosome to chromatin to generate AR-V7 (PMID:31647098), and a cytoplasmic interaction with eIF2α that restrains the unfolded protein response (PMID:30266800).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established that KDM4B is a bona fide enzyme that actively removes H3K9me3 in living cells, defining its core catalytic function before downstream biology could be assigned.

    Evidence Inducible Jmjd2b-GFP lines with SILAC heavy-methyl metabolic labeling and immunofluorescence at pericentric heterochromatin

    PMID:16738407

    Open questions at the time
    • Poor in vitro activity left the physiological substrate kinetics unresolved
    • Did not address gene-specific transcriptional consequences
  2. 2008 High

    Identified KDM4B as a direct HIF-1α transcriptional target, placing the demethylase downstream of hypoxic signaling.

    Evidence ChIP of HIF-1α at the JMJD2B promoter, reporter assays, and demethylase activity confirmation under hypoxia

    PMID:18984585

    Open questions at the time
    • Downstream genes regulated by hypoxia-induced KDM4B not mapped here
  3. 2010 Medium

    Defined how KDM4B finds its substrate, showing localization depends on its reader domains and on SUV39h-generated H3K9me3.

    Evidence GFP-fusion live-cell imaging, FRAP, and truncation/point mutants in SUV39h-deficient cells

    PMID:21073875

    Open questions at the time
    • Did not establish whether reader-domain mutants disrupt catalytic turnover
    • Mobility measured only at chromocenters
  4. 2012 High

    Connected H3K9me3 removal to specific differentiation programs, showing KDM4B activates DLX (osteogenesis), adipogenic, and cell-cycle gene loci as a transcription-factor cofactor.

    Evidence ChIP, Co-IP, EMSA, reporter assays and in vivo ovariectomized/aging mouse models in MSCs and 3T3-L1 cells

    PMID:22722334 PMID:22770241

    Open questions at the time
    • Mechanism of recruitment to individual TF complexes not fully separated from genome-wide effects
  5. 2013 High

    Revealed KDM4B as a multi-functional transcriptional coactivator across nuclear-receptor and lineage pathways and a DNA-damage-response factor, including a catalysis-independent role in stabilizing AR protein.

    Evidence Co-IP, ChIP, ubiquitination assays, demethylase-dead mutants, laser micro-irradiation with PARP inhibition (ERα/MLL2, AR, GATA-3, β-catenin, DSB systems)

    PMID:21445275 PMID:21502505 PMID:23435229 PMID:23723241 PMID:23744078 PMID:24077348

    Open questions at the time
    • Whether the H3K4/H3K9 mark coordination is direct or sequential at single loci not resolved
    • Catalysis-independent AR stabilization mechanism (E3 ligase blocked) not identified
  6. 2013 Medium

    Placed KDM4B in a p53 feedback circuit, linking the demethylase both to attenuation of p53 transcriptional output and to heterochromatin repair after DNA damage.

    Evidence ChIP of p53 at the JMJD2B promoter, siRNA, reporters, IR survival assays

    PMID:23376847 PMID:28073943

    Open questions at the time
    • Single-lab studies; physiological context of the p53–KDM4B loop in normal tissue unclear
  7. 2013 High

    Showed KDM4B is required for pluripotency and reprogramming, integrating it into the core Nanog regulatory network.

    Evidence RNAi screen, genome-wide ChIP-seq occupancy, and iPS reprogramming assays in mouse ESCs

    PMID:24361252

    Open questions at the time
    • Degree of functional redundancy with KDM4C not fully partitioned
  8. 2014 High

    Solved the catalytic architecture, providing a structural basis for K9/K36 selectivity and a template for inhibitor design.

    Evidence X-ray crystallography of the KDM4B/2,4-PDCA/H3K9me3 ternary complex with inhibition and ChIP validation

    PMID:24971742

    Open questions at the time
    • Structure of full-length enzyme with reader domains not determined
  9. 2014 Medium

    Mapped the Hsp90 chaperone and β-catenin/MyoD interactions, defining post-translational stabilization and additional lineage-specific coactivator roles.

    Evidence Co-IP, ubiquitination-site mutagenesis (K337/K562), geldanamycin treatment, domain mapping, ChIP and rescue in myoblasts

    PMID:23589305 PMID:24481461 PMID:25534856

    Open questions at the time
    • The cognate E3 ligase for basal/geldanamycin-induced ubiquitination not identified here
  10. 2018 High

    Uncovered non-canonical cytoplasmic and degradation-control functions: restraint of eIF2α phosphorylation/UPR and SCF^Fbxo22-dependent degradation that underlies tamoxifen antagonism.

    Evidence Cytoplasmic Co-IP with eIF2α, UPR/apoptosis assays, ubiquitination assays, live-cell FRET/BiFC and ChIP in ERα systems

    PMID:30266800 PMID:30418174

    Open questions at the time
    • How demethylase activity is required for a cytoplasmic eIF2α function is mechanistically unexplained
    • Substrate(s) bridging KDM4B to Fbxo22 recognition not fully defined
  11. 2019 High

    Defined a chromatin-coupled splicing scaffold activity, showing PKA-phosphorylated KDM4B binds SF3B3 and AR pre-mRNA to generate the AR-V7 variant driving castration resistance.

    Evidence IP, RIP, ATAC-seq, genome-wide splicing profiling and phosphorylation mapping

    PMID:31647098

    Open questions at the time
    • Generality of the splicing-scaffold role beyond AR not tested
    • Relationship between this activity and demethylase catalysis unresolved
  12. 2021 High

    Extended KDM4B into telomere maintenance and bone remodeling, showing its inactivation drives ALT and its complex with CCAR1/MED1 recruits NF-κB p65 for osteoclastogenesis.

    Evidence Genetic KO/overexpression in ESC and ALT models; ChIP-seq, Co-IP, myeloid conditional KO and inhibitor treatment

    PMID:33571444 PMID:33972520 PMID:34031372

    Open questions at the time
    • Direct molecular link between KDM4B loss and the ALT recombination machinery not delineated
  13. 2024 Medium

    Completed the regulatory loop around KDM4B stability and angiogenic output, adding UCHL1 deubiquitination and an m6A/WTAP mRNA-stabilization axis upstream, with VEGFA/HIF2α downstream.

    Evidence Ubiquitination assays with UCHL1 catalytic mutant, m6A-seq, mRNA stability assays, ChIP at VEGFA promoter, xenografts

    PMID:37087529 PMID:38743986

    Open questions at the time
    • Single-lab studies; interplay of competing stabilizing/destabilizing inputs not integrated quantitatively

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KDM4B's distinct activities—nuclear demethylase, DSB-repair factor, cytoplasmic eIF2α regulator, and splicing scaffold—are selected in a given cell state, and which inputs dominate its competing stabilization/degradation pathways, remains unresolved.
  • No unified model integrating catalytic and non-catalytic functions
  • Determinants of nuclear vs cytoplasmic partitioning unknown
  • Quantitative hierarchy among Hsp90/Fbxo22/ERK/UCHL1/m6A regulation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0016491 oxidoreductase activity 2 GO:0003723 RNA binding 1 GO:0042393 histone binding 1
Localization
GO:0005654 nucleoplasm 3 GO:0000228 nuclear chromosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-73894 DNA Repair 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
ARCEBPBCTNNB1EIF2AKESR1GATA3HSP90MYOD1
Complex memberships
JMJD2B-TFAP2C-LSD1 complexKDM4B-CCAR1-MED1 complexMLL2 H3K4 methyltransferase complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Jmjd2b (KDM4B) actively removes H3K9me3 at pericentric heterochromatin in mammalian cells; metabolic labeling with heavy methyl groups demonstrated this is an active demethylation process occurring before DNA replication. Recombinant Jmjd2b appeared as a poor enzyme in vitro, yet also reduced H3K36 methylation. Inducible Jmjd2b-GFP cell lines, metabolic labeling with heavy methyl groups (SILAC-based), immunofluorescence Genes & development High 16738407
2011 JMJD2B (KDM4B) is an integral component of the MLL2 H3K4 methyltransferase complex and co-purifies with estrogen receptor α (ERα). H3K9 demethylation by JMJD2B is a prerequisite for H3K4 methylation at ERα target gene promoters, coordinating the mutual exclusivity of H3K9 and H3K4 methylation during ERα-activated transcription. Affinity purification/co-purification, ChIP, siRNA knockdown, in vitro transcription assays, xenograft tumor assay Proceedings of the National Academy of Sciences of the United States of America High 21502505
2011 JMJD2B (KDM4B) interacts with ERα and components of the SWI/SNF-B chromatin remodeling complex; it is recruited to ERα target sites where it demethylates H3K9me3 to facilitate transcription of ER-responsive genes including MYB, MYC, and CCND1. Co-immunoprecipitation, ChIP, siRNA knockdown, mammary gland-specific conditional knockout mice PloS one High 21445275
2008 HIF-1α directly binds recognition sites in the JMJD2B gene promoter and induces its transcription under hypoxia; ectopically expressed JMJD2B retains histone lysine demethylase activity under hypoxic conditions. ChIP, reporter assay, qRT-PCR, Western blot, ectopic expression with demethylase activity assay The Journal of biological chemistry High 18984585
2013 KDM4B enzymatic (demethylase) activity is required to enhance androgen receptor (AR) transcriptional activity; independently of demethylase activity, KDM4B enhances AR protein stability by inhibiting AR ubiquitination. Knockdown of KDM4B causes near-complete depletion of AR protein. KDM4B is itself androgen-regulated. siRNA screen, co-immunoprecipitation, ubiquitination assay, luciferase reporter, Western blot Nucleic acids research High 23435229
2014 Crystal structure of KDM4B in ternary complex with pyridine 2,4-dicarboxylic acid and H3K9me3 peptide was solved, revealing the active-site architecture and a selective K9/K36 binding site. Pharmacological and genetic inhibition of KDM4B increased H3K9me3 and silenced growth-related AR-responsive genes. X-ray crystallography, virtual screening, in vitro enzymatic inhibition assay, ChIP, cell viability assay Journal of medicinal chemistry High 24971742
2013 KDM4B controls expression of ER and FOXA1 genes by demethylating repressive H3K9me3 marks in their upstream regulatory regions, enabling GATA-3 binding. KDM4B physically interacts with GATA-3 in breast cancer cells and co-activates GATA-3 transcriptional activity. Co-immunoprecipitation, ChIP, luciferase reporter, siRNA knockdown Nucleic acids research Medium 23723241
2013 Kdm4b is rapidly recruited to DNA double-strand breaks induced by laser micro-irradiation in a PARP1-dependent and demethylase-activity-dependent manner. Overexpression of Kdm4b decreased γH2AX foci 6 hours after γ-irradiation and increased cell survival. H3K9me2/3 levels decreased at early time points after γ-irradiation. Laser micro-irradiation, live-cell imaging (EGFP fusion), PARP inhibitor treatment, γH2AX foci quantification, clonogenic survival assay The Journal of biological chemistry High 23744078
2012 KDM4B promotes osteogenic commitment of MSCs by removing repressive H3K9me3 at DLX gene loci, thereby activating DLX expression. KDM6B acts in parallel on H3K27me3/HOX. Depletion of KDM4B shifts MSCs toward adipogenesis. shRNA knockdown, ChIP, differentiation assays (osteogenic/adipogenic), ovariectomized and aging mouse models Cell stem cell High 22770241
2013 Jmjd2b and Jmjd2c (KDM4C) are necessary for self-renewal of mouse ESCs and iPS cell generation. Genome-wide occupancy reveals Jmjd2b-unique target sites belong to the Core (Nanog) regulatory module; Jmjd2b and Nanog act through an interconnected regulatory loop. RNAi screen, genome-wide ChIP-seq occupancy, iPS reprogramming assays Molecular cell High 24361252
2013 Heat shock protein Hsp90 physically interacts with and stabilizes KDM4B protein. Pharmacological Hsp90 inhibition with geldanamycin causes ubiquitin-dependent proteasomal degradation of KDM4B (but not KDM4C). KDM4B is ubiquitinated on lysines 337 and 562; simultaneous K337R/K562R substitution suppresses geldanamycin-induced degradation. Co-immunoprecipitation, pharmacological inhibition (geldanamycin), ubiquitination assay, site-directed mutagenesis The Journal of biological chemistry High 23589305
2012 Histone demethylase Kdm4b acts as a co-factor of C/EBPβ during mitotic clonal expansion (MCE) of 3T3-L1 preadipocytes. Kdm4b expression is induced by C/EBPβ binding to its promoter; Kdm4b interacts with C/EBPβ, is recruited to promoters of C/EBPβ-regulated cell cycle genes (Cdc45l, Mcm3, Gins1, Cdc25c), demethylates H3K9me3 there, and activates their transcription. ChIP-on-chip, EMSA, luciferase assay, co-immunoprecipitation, siRNA knockdown, ChIP Cell death and differentiation High 22722334
2013 p53 directly induces JMJD2B gene expression by binding a canonical p53 consensus motif in the JMJD2B promoter. JMJD2B induction attenuates transcription of p53 targets (p21, PIG3, PUMA) in a catalytic-activity-dependent manner, forming a negative auto-regulatory feedback loop on p53 transcriptional output. ChIP, siRNA knockdown, luciferase reporter, gain/loss-of-function, xenograft tumor assay Nucleic acids research Medium 28073943
2013 p53 directly induces JMJD2b expression through promoter binding, leading to reduction of H3K9me3 at pericentric heterochromatin after DNA damage. JMJD2b depletion delays slow-phase HC DNA repair and reduces clonogenic survival after ionizing irradiation. ChIP, siRNA knockdown, IR survival assay, Western blot Oncogene Medium 23376847
2015 TGF-β induces KDM4B expression in MSCs; KDM4B is recruited to the SOX9 promoter, removes H3K9me3, and activates SOX9 transcription. KDM4B depletion reduces SMAD3 occupancy at the SOX9 promoter, establishing KDM4B as required for SMAD-dependent coactivation of SOX9 during chondrogenesis. ChIP, shRNA knockdown, overexpression, differentiation assays Stem cells (Dayton, Ohio) Medium 26485430
2019 KDM4B is phosphorylated by protein kinase A (PKA) under castration-resistance–promoting conditions, enabling its binding to splicing factor SF3B3. KDM4B binds RNA near the 5'-CE3 region of AR pre-mRNA, increases chromatin accessibility, and couples the spliceosome to chromatin to promote inclusion of CE3, generating the AR-V7 splice variant. Immunoprecipitation, RNA immunoprecipitation, ATAC-seq, genome-wide splicing profiling, phosphorylation assay Nucleic acids research High 31647098
2018 SCF^Fbxo22 ubiquitylates KDM4B complexed with tamoxifen-bound ERα, leading to KDM4B degradation and release of steroid receptor coactivator (SRC) from ER. This Fbxo22-dependent KDM4B degradation is required for tamoxifen antagonist activity; Fbxo22 depletion restores ER-dependent transcription via AF1 even in SERM-treated cells. Co-immunoprecipitation, ubiquitination assay, live-cell fluorescence imaging (FRET/BiFC), ChIP, in vitro and in vivo tumor growth The Journal of clinical investigation High 30418174
2014 KDM4B forms complexes with β-catenin in vitro and in vivo (involving KDM4B amino acids 353–740) and also interacts with TCF4. KDM4B co-occupies β-catenin/TCF4 target gene promoters, and its knockdown reduces expression of JUN, MYC, and Cyclin D1. Co-immunoprecipitation (in vitro and in vivo), ChIP, siRNA knockdown, clonogenic assay International journal of oncology Medium 24481461
2013 JMJD2B physically associates with β-catenin and enhances its nuclear localization and transcriptional activity in gastric cancer cells. JMJD2B binds the vimentin promoter together with β-catenin and induces local H3K9 demethylation to activate vimentin transcription, promoting EMT. Co-immunoprecipitation, ChIP, siRNA knockdown, invasion/migration assays, in vivo metastasis Clinical cancer research Medium 24077348
2015 In chick embryo, KDM4B dynamically occupies regulatory regions of the Dlx3 locus and removes H3K9me3 to activate Dlx3 expression; loss of KDM4B causes defective otic vesicle invagination. A catalytically dead KDM4B mutant fails to rescue the invagination phenotype, whereas DLX3 co-electroporation rescues it, placing KDM4B upstream of DLX3 in otic placode invagination. In vivo ChIP, electroporation/knockdown in chick embryo, rescue with catalytic-dead mutant The Journal of cell biology High 26598618
2021 Loss of KDM4B in MSCs increases H3K9me3 and impairs β-catenin/Smad1-mediated transcription. KDM4B ablation induces senescence-associated heterochromatin foci formation and promotes MSC exhaustion. KDM4B is required for parathyroid hormone-mediated bone anabolic signaling. Conditional knockout mice, ChIP, differentiation assays, senescence assays Cell stem cell High 33571444
2021 KDM4B physically and functionally associates with CCAR1 and MED1 in a complex. This KDM4B-CCAR1-MED1 complex localizes to promoters of osteoclast-related genes upon RANKL stimulation, induces H3K9 demethylation (euchromatinization), and recruits NF-κB p65 via a direct interaction between KDM4B and p65. Co-immunoprecipitation, genome-wide ChIP-seq, conditional KO mice (myeloid-specific), in vivo KDM4B inhibitor treatment Bone research High 34031372
2021 Inactivation of KDM4B (via H3.3G34R or IDH1/2 mutations) cooperates with ATRX loss to drive Alternative Lengthening of Telomeres (ALT) in glioblastoma. KDM4B overexpression in ALT cancer cells abrogates ALT-associated features, identifying KDM4B as the key demethylase whose inactivation promotes ALT. Mouse ESC genetic KO (ATRX, TP53, TERT, KDM4B), KDM4B overexpression in ALT cells, telomere characterization Nature communications High 33972520
2018 KDM4B interacts with eIF2α in the cytoplasm and maintains reduced phosphorylation of eIF2α; this cytoplasmic function is independent of its canonical histone demethylase role but requires demethylase activity. KDM4B depletion or inhibition activates the unfolded protein response (UPR) and causes preferential apoptosis in PTEN-deficient triple-negative breast cancers. Co-immunoprecipitation (cytoplasmic fraction), siRNA/small molecule inhibition, UPR pathway activation assays, apoptosis assays The Journal of experimental medicine Medium 30266800
2017 KDM4B activates LINE-1 retrotransposons by removing H3K9me3 from evolutionarily young LINE-1 elements genome-wide. KDM4B overexpression enhances LINE-1 retrotransposition efficacy, copy number, and associated DNA damage in breast cancer cells. Genome-wide H3K9me3 ChIP-seq, LINE-1 retrotransposition assay, copy number analysis, KDM4B inhibitor treatment Cancer research Medium 30459150
2019 N-Myc physically interacts with and recruits KDM4B in neuroblastoma cells. KDM4B regulates Myc pathway target genes and neuroblastoma cell proliferation and differentiation in vitro and xenograft growth in vivo. Immunoprecipitation, immunofluorescence, ChIP, shRNA knockdown, xenograft Journal of the National Cancer Institute Medium 25925418
2017 JMJD2B activity controls autophagy via epigenetic regulation of LC3B (MAP1LC3B) gene expression; JMJD2B knockdown reduces H3K9 demethylation at the LC3B promoter and decreases autophagy, reducing intracellular amino acid availability under glucose deprivation in colorectal cancer cells. ChIP, siRNA knockdown, metabolic profiling, xenograft, immunofluorescence, electron microscopy Theranostics Medium 32483417
2019 KDM4B physically interacts with c-Jun and co-occupies the IL-8, MMP1, and ITGAV promoters; demethylase activity is required for KDM4B-mediated upregulation of these targets. KDM4B depletion reduces integrin αV expression and impairs H. pylori-induced cell migration. Co-immunoprecipitation, ChIP, demethylase-dead mutant analysis, siRNA knockdown Cell death & disease Medium 30683841
2021 KDM4B physically interacts with c-Myc; the KDM4B-c-Myc complex is co-recruited to c-Myc-binding sequences on promoters of metabolic genes (LDHA, ENO1, PFK) and synergistically promotes transactivation of LDHA in a demethylase-dependent manner. Co-immunoprecipitation, reporter assay, ChIP, Seahorse metabolic flux analysis, metabolomics Theranostics Medium 34335964
2017 JMJD2B promotes adipogenesis by removing H3K9me2/3 from the promoters of PPARγ and C/EBPα, activating their expression during 3T3-L1 differentiation. ChIP, siRNA knockdown, overexpression, adipogenesis assays PloS one Medium 28060835
2018 JMJD2B removes H3K9me2/3 from the PPARγ2 promoter to activate its expression and downstream lipogenic target genes, promoting hepatic steatosis. JMJD2B interacts with activated LXRα and is recruited to LXR response elements (LXRE), reducing H3K9me2/3 there to activate LXRα-dependent lipogenesis. ChIP, co-immunoprecipitation, adenoviral overexpression, siRNA knockdown, reporter assay, in vivo mouse model Scientific reports / International journal of molecular sciences Medium 30214048 33167594
2016 Neuron-specific deletion of Jmjd2b in mice causes increased total spine number but decreased mature spines in hippocampal CA1, hyperactive behavior, working memory deficits, and spontaneous epileptic-like seizures, establishing KDM4B as a required epigenetic regulator of functional neural circuit development. Cre-loxP conditional knockout, spine morphology analysis, behavioral testing (open field, maze), EEG Translational psychiatry Medium 27023172
2020 JMJD2B is induced by TGF-β2 and EndMT-promoting/hypoxic conditions in endothelial cells; it mediates site-specific H3K9me3 removal at promoters of mesenchymal genes (CNN1) and TGF-β signaling genes (AKT3, SULF1) to drive endothelial-to-mesenchymal transition. Endothelial-specific deletion of JMJD2B in vivo reduces EndMT after myocardial infarction. siRNA knockdown, endothelial-specific conditional KO mice, ChIP, endothelial barrier assay Proceedings of the National Academy of Sciences of the United States of America High 32034099
2017 p-ERK phosphorylates JMJD2B at Thr305, Ser352, Ser566, and Thr1065 under glucose deprivation, stabilizing JMJD2B by protecting it from ubiquitination and proteasomal degradation. The interaction between JMJD2B and p-ERK increases under glucose deprivation. Co-immunoprecipitation, immunoprecipitation/Western blot for phosphorylation, ubiquitination assay, cell viability assay Oncogene Medium 28945223
2020 KDM4B interacts with TRAF6 and promotes TRAF6-mediated K63-linked ubiquitination of AKT, leading to AKT activation and upregulation of GLUT1 expression, thereby promoting glucose uptake in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, ChIP, glucose uptake assay Journal of experimental & clinical cancer research Medium 31931846
2012 Inducible expression of JMJD2B in mouse ES cells decreased total H3K9me3 by 63%. When these H3K9me3-reduced cells were used as nuclear transfer donors, H3K9me3 was normalized within minutes following fusion with enucleated oocytes, and development into cloned embryos improved by 30%. Inducible transgenic ES cells, nuclear transfer, immunofluorescence, embryo development assay Molecular and cellular biology Medium 23263990
2014 KDM4B interacts with MyoD in C2C12 myoblast cells, is recruited to MyoD and myogenin promoters, and demethylates H3K9me3 there, activating their transcription. Depletion of KDM4B inhibits myogenic differentiation, which is rescued by exogenous MyoD. Co-immunoprecipitation, ChIP, shRNA knockdown, luciferase reporter, overexpression rescue Biochemical and biophysical research communications Medium 25534856
2021 JMJD2B/KDM4B forms a protein complex with AP-2 family transcription factor TFAP2C and histone demethylase LSD1 in trophoblast stem cells. This complex predominantly occupies active gene promoters. JMJD2B is also associated with loss of H3K36me3 at a subset of embryonic lineage genes marked by H3K9me3 for stable repression. ChIP-seq, transcriptome analysis, co-immunoprecipitation, siRNA knockdown Scientific reports Medium 33441614
2023 HIF1α transcriptionally activates WTAP, a component of the m6A methyltransferase complex, which in turn increases m6A modification on KDM4B mRNA, stabilizing it. This establishes a HIF1α→WTAP→m6A-KDM4B axis coupling RNA methylation to histone demethylation (H3K9me3) in AML. ChIP, m6A-seq, mRNA stability assay, siRNA/shRNA knockdown, in vivo xenograft Leukemia Medium 37087529
2024 The deubiquitinase UCHL1 mediates deubiquitination of KDM4B, stabilizing its protein levels. KDM4B binds directly to the VEGFA promoter, removes H3K9me3, and cooperates with HIF2α to activate VEGFA transcription, promoting angiogenesis and bevacizumab resistance in clear cell renal cell carcinoma. In vivo ubiquitination assay, co-immunoprecipitation, ChIP, luciferase reporter, UCHL1 C90A catalytic mutant Translational oncology Medium 38743986
2019 KDM3A and KDM4B co-operate in an auto-regulatory loop in ERα-positive breast cancer; KDM3A primes chromatin for FOXA1 and ER-complex recruitment prior to ER binding. Combined depletion of KDM3A and KDM4B has a greater inhibitory effect on ER activity and cell growth than either alone. ChIP, siRNA knockdown (individual and combined), global gene expression analysis Cancers Medium 31390833
2010 Full-length JMJD2b-GFP localizes to chromocenters in a manner dependent on SUV39h (its substrate-generating methyltransferase); in SUV39h-deficient cells, chromocenter localization is reduced alongside global H3K9me3 decrease. PHD Zn-finger and Tudor domains of JMJD2b are required for correct chromocenter localization. FRAP reveals ~50% mobile fraction with <1 s recovery; SUV39h deficiency increases the mobile fraction. GFP fusion live-cell imaging, FRAP, SUV39h knockout cells, truncation/point-mutation analysis Journal of molecular biology Medium 21073875
2017 KDM4B is recruited to the ICAM1 and VCAM1 promoters upon TNF-α stimulation, removes H3K9me2, and is required for TNF-α-induced upregulation of these vascular adhesion molecules and subsequent leukocyte adhesion/transmigration in brain microvascular endothelial cells. ChIP, siRNA knockdown, KDM4 inhibitor (ML324), leukocyte adhesion/transmigration assay, in vivo neutrophil adhesion Scientific reports Medium 28327608
2019 JMJD2B depletion causes spontaneous DNA double-strand breaks and radiosensitizes colorectal cancer cells through suppression of STAT3 signaling; STAT3 overexpression in KDM4B-knockdown cells attenuates DNA damage and restores cell survival. CREB transcription factor directly binds the KDM4B promoter to drive its expression. ChIP, siRNA knockdown/overexpression, γH2AX foci, STAT3 pathway western blot, clonogenic assay Molecular and cellular biochemistry Low 29633065

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes & development 303 16738407
2012 Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs. Cell stem cell 286 22770241
2008 The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. The Journal of biological chemistry 284 18984585
2011 Histone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 216 21502505
2011 Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development. PloS one 157 21445275
2010 The histone demethylase JMJD2B is regulated by estrogen receptor alpha and hypoxia, and is a key mediator of estrogen induced growth. Cancer research 153 20682797
2021 Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging. Cell stem cell 142 33571444
2013 Kdm4b histone demethylase is a DNA damage response protein and confers a survival advantage following γ-irradiation. The Journal of biological chemistry 126 23744078
2013 The lysine demethylase, KDM4B, is a key molecule in androgen receptor signalling and turnover. Nucleic acids research 106 23435229
2013 Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Molecular cell 105 24361252
2020 Enterotoxigenic Bacteroides fragilis induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B. Gut microbes 99 32684087
2013 JMJD2B promotes epithelial-mesenchymal transition by cooperating with β-catenin and enhances gastric cancer metastasis. Clinical cancer research : an official journal of the American Association for Cancer Research 95 24077348
2019 IL-6 and sIL-6R induces STAT3-dependent differentiation of human VSMCs into osteoblast-like cells through JMJD2B-mediated histone demethylation of RUNX2. Bone 91 30981888
2014 KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor. Journal of medicinal chemistry 84 24971742
2012 HIF-1α-induced histone demethylase JMJD2B contributes to the malignant phenotype of colorectal cancer cells via an epigenetic mechanism. Carcinogenesis 76 22745382
2013 KDM4B is a master regulator of the estrogen receptor signalling cascade. Nucleic acids research 71 23723241
2011 Histone demethylase JMJD2B is required for tumor cell proliferation and survival and is overexpressed in gastric cancer. Biochemical and biophysical research communications 65 22133676
2011 The histone demethylase JMJD2B plays an essential role in human carcinogenesis through positive regulation of cyclin-dependent kinase 6. Cancer prevention research (Philadelphia, Pa.) 60 21930796
2015 The role of histone demethylase KDM4B in Myc signaling in neuroblastoma. Journal of the National Cancer Institute 59 25925418
2013 p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression. Oncogene 57 23376847
2012 Histone demethylase Kdm4b functions as a co-factor of C/EBPβ to promote mitotic clonal expansion during differentiation of 3T3-L1 preadipocytes. Cell death and differentiation 57 22722334
2019 Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation. Nucleic acids research 56 31647098
2015 Transforming Growth Factor-β-Induced KDM4B Promotes Chondrogenic Differentiation of Human Mesenchymal Stem Cells. Stem cells (Dayton, Ohio) 56 26485430
2012 Transient JMJD2B-mediated reduction of H3K9me3 levels improves reprogramming of embryonic stem cells into cloned embryos. Molecular and cellular biology 55 23263990
2018 KDM4B protects against obesity and metabolic dysfunction. Proceedings of the National Academy of Sciences of the United States of America 52 29844188
2016 The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer. Oncogene 52 27869162
2020 The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition. Proceedings of the National Academy of Sciences of the United States of America 49 32034099
2020 KDM4B facilitates colorectal cancer growth and glucose metabolism by stimulating TRAF6-mediated AKT activation. Journal of experimental & clinical cancer research : CR 47 31931846
2018 Fbxo22-mediated KDM4B degradation determines selective estrogen receptor modulator activity in breast cancer. The Journal of clinical investigation 47 30418174
2019 KDM4B: A Nail for Every Hammer? Genes 46 30759871
2014 Stimulation of β-catenin and colon cancer cell growth by the KDM4B histone demethylase. International journal of oncology 46 24481461
2021 Mutations inhibiting KDM4B drive ALT activation in ATRX-mutated glioblastomas. Nature communications 44 33972520
2015 miR-491-5p functions as a tumor suppressor by targeting JMJD2B in ERα-positive breast cancer. FEBS letters 44 25725194
2021 Targeting KDM4B that coactivates c-Myc-regulated metabolism to suppress tumor growth in castration-resistant prostate cancer. Theranostics 41 34335964
2018 KDM4B-regulated unfolded protein response as a therapeutic vulnerability in PTEN-deficient breast cancer. The Journal of experimental medicine 38 30266800
2012 Histone demethylase JMJD2B-mediated cell proliferation regulated by hypoxia and radiation in gastric cancer cell. Biochimica et biophysica acta 37 23046878
2011 Triptolide induces cell-cycle arrest and apoptosis of human multiple myeloma cells in vitro via altering expression of histone demethylase LSD1 and JMJD2B. Acta pharmacologica Sinica 37 22120968
2018 Histone Demethylase KDM4B Promotes DNA Damage by Activating Long Interspersed Nuclear Element-1. Cancer research 36 30459150
2017 KDM4B-mediated epigenetic silencing of miRNA-615-5p augments RAB24 to facilitate malignancy of hepatoma cells. Oncotarget 36 27487123
2017 Role of JMJD2B in colon cancer cell survival under glucose-deprived conditions and the underlying mechanisms. Oncogene 35 28945223
2019 KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis. Cell death & disease 34 30683841
2019 Upregulated KDM4B promotes prostate cancer cell proliferation by activating autophagy. Journal of cellular physiology 34 31468537
2018 Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2. Scientific reports 34 30214048
2007 Comparative integromics on JMJD2A, JMJD2B and JMJD2C: preferential expression of JMJD2C in undifferentiated ES cells. International journal of molecular medicine 34 17611647
2021 MicroRNA-15a Carried by Mesenchymal Stem Cell-Derived Extracellular Vesicles Inhibits the Immune Evasion of Colorectal Cancer Cells by Regulating the KDM4B/HOXC4/PD-L1 Axis. Frontiers in cell and developmental biology 33 33732698
2017 Histone H3K9 Demethylase JMJD2B Activates Adipogenesis by Regulating H3K9 Methylation on PPARγ and C/EBPα during Adipogenesis. PloS one 33 28060835
2017 KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. Nucleic acids research 33 28073943
2020 Histone H3K9 Demethylase JMJD2B Plays a Role in LXRα-Dependent Lipogenesis. International journal of molecular sciences 32 33167594
2017 KDM4B-mediated reduction of H3K9me3 and H3K36me3 levels improves somatic cell reprogramming into pluripotency. Scientific reports 32 28790329
2016 Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse. Translational psychiatry 32 27023172
2013 Heat shock protein 90 (Hsp90) selectively regulates the stability of KDM4B/JMJD2B histone demethylase. The Journal of biological chemistry 31 23589305
2020 Targeting the KDM4B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate cancer. The Journal of pathology 30 32617978
2016 JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression. Oncotarget 30 27232941
2022 The Diverse Roles of Histone Demethylase KDM4B in Normal and Cancer Development and Progression. Frontiers in cell and developmental biology 29 35186950
2015 Emodin attenuates radioresistance induced by hypoxia in HepG2 cells via the enhancement of PARP1 cleavage and inhibition of JMJD2B. Oncology reports 29 25607726
2021 The KDM4B-CCAR1-MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis. Bone research 28 34031372
2020 JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy. Theranostics 27 32483417
2018 MiRNA-491-5p inhibits cell proliferation, invasion and migration via targeting JMJD2B and serves as a potential biomarker in gastric cancer. American journal of translational research 27 29511447
2015 KDM4B promotes epithelial-mesenchymal transition through up-regulation of ZEB1 in pancreatic cancer. Acta biochimica et biophysica Sinica 27 26511091
2018 Distal-less homeobox 5 promotes the osteo-/dentinogenic differentiation potential of stem cells from apical papilla by activating histone demethylase KDM4B through a positive feedback mechanism. Experimental cell research 26 30503866
2017 KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels. Scientific reports 26 28327608
2015 KDM4A, KDM4B and KDM4C in non-small cell lung cancer. International journal of clinical and experimental pathology 26 26722485
2014 Silencing of JMJD2B induces cell apoptosis via mitochondria-mediated and death receptor-mediated pathway activation in colorectal cancer. Journal of digestive diseases 26 24957706
2020 Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects. American journal of human genetics 25 33232677
2016 KDM4B plays an important role in mitochondrial apoptosis by upregulating HAX1 expression in colorectal cancer. Oncotarget 25 27506941
2015 KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1. Oncotarget 25 26397136
2018 KDM4B promotes DNA damage response via STAT3 signaling and is a target of CREB in colorectal cancer cells. Molecular and cellular biochemistry 24 29633065
2018 Hypoxia and Hormone-Mediated Pathways Converge at the Histone Demethylase KDM4B in Cancer. International journal of molecular sciences 23 29342868
2018 Inhibition of the histone demethylase KDM4B leads to activation of KDM1A, attenuates bacterial-induced pro-inflammatory cytokine release, and reduces osteoclastogenesis. Epigenetics 23 29927684
2023 HIF1α-mediated transactivation of WTAP promotes AML cell proliferation via m6A-dependent stabilization of KDM4B mRNA. Leukemia 22 37087529
2017 Heterochromatin Reduction Correlates with the Increase of the KDM4B and KDM6A Demethylases and the Expression of Pericentromeric DNA during the Acquisition of a Transformed Phenotype. Journal of Cancer 22 28928876
2018 JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities. Genes to cells : devoted to molecular & cellular mechanisms 21 30073721
2018 KDM4B promotes gastric cancer metastasis by regulating miR-125b-mediated activation of Wnt signaling. Journal of cellular biochemistry 21 30485532
2019 The Histone Demethylase Enzymes KDM3A and KDM4B Co-Operatively Regulate Chromatin Transactions of the Estrogen Receptor in Breast Cancer. Cancers 20 31390833
2015 Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression. The Journal of cell biology 19 26598618
2012 TSA-induced JMJD2B downregulation is associated with cyclin B1-dependent survivin degradation and apoptosis in LNCap cells. Journal of cellular biochemistry 19 22388778
2021 Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells. Frontiers in cell and developmental biology 18 34249900
2014 JMJD2B as a potential diagnostic immunohistochemical marker for hepatocellular carcinoma: a tissue microarray-based study. Acta histochemica 18 25533242
2016 Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma. Anticancer research 17 27630312
2015 Histone demethylase JMJD2B and JMJD2C induce fibroblast growth factor 2: mediated tumorigenesis of osteosarcoma. Medical oncology (Northwood, London, England) 17 25636512
2020 Osmolarity controls the differentiation of adipose-derived stem cells into nucleus pulposus cells via histone demethylase KDM4B. Molecular and cellular biochemistry 16 32594337
2014 The histone demethylase KDM4B interacts with MyoD to regulate myogenic differentiation in C2C12 myoblast cells. Biochemical and biophysical research communications 16 25534856
2020 Inhibition of microRNA-27b-3p relieves osteoarthritis pain via regulation of KDM4B-dependent DLX5. BioFactors (Oxford, England) 15 32856377
2012 Functional analysis of histone demethylase Jmjd2b on lipopolysaccharide-treated murine neural stem cells (NSCs). Neurotoxicity research 15 22890720
2022 Histone H3K9 demethylase JMJD2B/KDM4B promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating H3K9me2 on RUNX2. PeerJ 14 36217382
2021 Histone demethylase JMJD2B/KDM4B regulates transcriptional program via distinctive epigenetic targets and protein interactors for the maintenance of trophoblast stem cells. Scientific reports 14 33441614
2024 circBRAF promotes the progression of triple-negative breast cancer through modulating methylation by recruiting KDM4B to histone H3K9me3 and IGF2BP3 to mRNA. American journal of cancer research 12 38859856
2019 The histone demethylase JMJD2B is critical for p53-mediated autophagy and survival in Nutlin-treated cancer cells. The Journal of biological chemistry 12 31036564
2023 KDM4B: A promising oncology therapeutic target. Cancer science 11 37923555
2023 Histone demethylase KDM4B accelerates the progression of glioblastoma via the epigenetic regulation of MYC stability. Clinical epigenetics 10 38093312
2021 Effects of demethylase KDM4B on the biological characteristics and function of yak cumulus cells in vitro. Theriogenology 10 34425304
2024 Super-enhancer-driven LncRNA PPARα-seRNA exacerbates glucolipid metabolism and diabetic cardiomyopathy via recruiting KDM4B. Molecular metabolism 9 38950776
2023 KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner. Molecular and cellular biochemistry 9 37249813
2022 Therapeutic targeting of histone lysine demethylase KDM4B blocks the growth of castration-resistant prostate cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 36495660
2010 Mutant genetic background affects the functional rearrangement and kinetic properties of JMJD2b histone demethylase. Journal of molecular biology 9 21073875
2024 H3K9me3 demethylation by JMJD2B is regulated by pirfenidone resulting in improved NASH. Scientific reports 8 39433954
2021 KDM4B Overexpression Promotes the Growth, Migration, and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Activating STAT3 Pathway. Biochemical genetics 8 33909202
2021 KDM4B promotes acute myeloid leukemia associated with AML1-ETO by regulating chromatin accessibility. FASEB bioAdvances 8 34938963
2024 Deubiquitinase UCHL1 stabilizes KDM4B to augment VEGF signaling and confer bevacizumab resistance in clear cell renal cell carcinoma. Translational oncology 7 38743986
2018 Histone demethylase KDM4A and KDM4B expression in granulosa cells from women undergoing in vitro fertilization. Journal of assisted reproduction and genetics 7 29536385

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