Affinage

KDM6B

Lysine-specific demethylase 6B · UniProt O15054

Length
1643 aa
Mass
176.6 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM6B (JMJD3) is an inducible histone H3K27me2/me3 demethylase that activates gene transcription by removing repressive polycomb marks at promoters, gene bodies, and enhancers, thereby licensing context-dependent transcriptional programs across development, immunity, metabolism, and disease (PMID:17713478, PMID:23243002). Its catalytic core converts H3K27me3 to lower methylation states, displacing polycomb proteins (PMID:17713478), and at TGF-β-responsive loci it acts not only at promoters but within gene bodies to facilitate elongating RNA Polymerase II progression (PMID:23243002). KDM6B is overwhelmingly deployed as a recruited cofactor: sequence-specific transcription factors and signaling effectors—including NF-κB (PMID:26802933), C/EBPβ (PMID:30135572), ISL1 and the Isl1-Lhx3 complex (PMID:27105846, PMID:35177643), KLF2 (PMID:31393857), KLF4 (PMID:33033262), HOXC9 (PMID:30631055), Smad2/3 (PMID:33414463), TFDP1 (PMID:35212626), and p53 (PMID:24797517)—physically engage KDM6B and direct it to specific enhancers and promoters where it erases H3K27me3 to drive lineage commitment, T-cell trafficking and differentiation, myeloid and metabolic gene programs, and tumor-associated transcription. Beyond catalysis, KDM6B operates through demethylase-independent mechanisms: it recruits the E3 ligase Trim26 to ubiquitinate and degrade PHF20 (PMID:23452852, PMID:33033262), scaffolds enhancer-promoter looping via the cohesin loading factor NIPBL (PMID:33033262), and activates MAPK-pathway genes (ELK1, FOS) and pro-differentiation AP-1/IER programs in a chromatin-modification-independent manner (PMID:28487543, PMID:30936419). KDM6B expression is itself a regulatory hub, induced or repressed by signaling inputs including TGF-β/activin-SMAD (PMID:23152497, PMID:26215835), interferon/JAK-STAT (PMID:28384648, PMID:32299951, PMID:33779682), vitamin D/VDR (PMID:21890490), and microRNA targeting (PMID:38218880), positioning it as a signal-responsive switch that couples extracellular cues to polycomb-controlled gene activation.

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2007 High

    Established the founding biochemical identity of KDM6B, answering whether it is an enzyme acting on chromatin and showing it actively reverses a repressive polycomb mark.

    Evidence In vitro demethylase assay, ectopic expression with H3K27me3 immunostaining, and C. elegans ortholog genetics

    PMID:17713478

    Open questions at the time
    • Did not define which transcription factors target the enzyme to specific loci
    • No structural basis for substrate selectivity
  2. 2011 Medium

    Connected KDM6B to upstream signaling and oncogenic induction, showing its expression is driven by VDR and the EBV oncogene LMP1 to control polycomb status at target genes.

    Evidence VDR-dependent induction with catalytic mutant and ChIP; LMP1 ectopic expression with H3K27me3 ChIP in lymphoma cells

    PMID:21242977 PMID:21890490

    Open questions at the time
    • Did not map the full target gene set
    • Mechanism of locus-specific recruitment not resolved
  3. 2012 High

    Defined the dual transcriptional logic of KDM6B in TGF-β responses—activating SNAI1 to drive EMT and acting within gene bodies to enable RNAPII elongation, not just initiation.

    Evidence Knockdown/overexpression with promoter ChIP and invasion assays; genome-wide ChIP-seq for JMJD3, elongating RNAPII, and H3K27me3

    PMID:23152497 PMID:23243002

    Open questions at the time
    • How JMJD3 couples to elongation machinery mechanistically not defined
    • EMT findings from a single lab
  4. 2013 High

    Revealed that KDM6B acts both catalytically and non-catalytically, including a demethylase-independent arm recruiting Trim26 to degrade PHF20, and showed it balances PRC2 to set lineage fates.

    Evidence iPSC reprogramming in Jmjd3-deficient MEFs with Co-IP, ubiquitination assays, catalytic mutants; embryo genetic manipulation with H3K27me3 ChIP at lineage loci; ESC mesoderm differentiation assays

    PMID:23452852 PMID:23671187 PMID:23856522

    Open questions at the time
    • How KDM6B selects PHF20 versus other substrates for Trim26 unclear
    • Stoichiometry of KDM6B vs PRC2 in fate decisions not quantified
  5. 2016 Medium

    Generalized KDM6B as a recruited transcription-factor cofactor by showing direct physical partnerships with NF-κB, ISL1, and p53 that target it to specific enhancers and promoters.

    Evidence Co-IP and ChIP/ChIP-seq with functional inactivation in keratinocyte wound healing, cardiac progenitors, and DNA-damage responses

    PMID:24797517 PMID:26802933 PMID:27105846

    Open questions at the time
    • Whether these interactions are direct or bridged is not always resolved
    • Domain requirements for each partnership incompletely mapped
  6. 2017 High

    Demonstrated catalysis-independent transcriptional activation as a bona fide mechanism, showing catalytically dead KDM6B still activates MAPK genes, and extended KDM6B roles to chondrocyte anabolism.

    Evidence CRISPR KO, RNA-seq, ChIP-qPCR and catalytically inactive mutant overexpression in myeloma; conditional cartilage KO with RNA-seq and OA models

    PMID:28314754 PMID:28487543

    Open questions at the time
    • The chromatin-independent effector mechanism on MAPK loci not defined
    • How KDM6B activates genes without modifying H3K27 is unresolved
  7. 2018 Medium

    Mapped KDM6B into metabolic and disease-specific transcriptional circuits, partnering with SIRT1/PPARα, IRF4, and C/EBPβ in feedback loops controlling β-oxidation, lymphoma survival, and myeloid differentiation.

    Evidence Co-IP, ChIP, liver-specific knockdown with metabolic phenotyping; demethylase-dependent rescue assays in DLBCL; Co-IP/RNA-seq/ChIP in AML

    PMID:27102442 PMID:29753027 PMID:29911994 PMID:30135572

    Open questions at the time
    • Gene-specificity determinants of SIRT1 partnership not defined
    • Whether feedback loops generalize beyond the studied systems unknown
  8. 2020 High

    Integrated the multiple mechanistic arms of KDM6B during reprogramming, showing KLF4-directed enhancer demethylation, NIPBL-dependent enhancer-promoter looping, elongation, and parallel PHF20 degradation.

    Evidence ChIP-seq for JMJD3/H3K27me3, Co-IP of JMJD3-KLF4 and JMJD3-NIPBL, looping analysis, and Trim26-PHF20 degradation assays during reprogramming

    PMID:33033262

    Open questions at the time
    • How NIPBL recruitment is mechanistically achieved by KDM6B is unresolved
    • Relative contribution of each arm to reprogramming not partitioned
  9. 2021 High

    Expanded KDM6B into chromatin-architecture and stress-adaptive immune/metabolic programs, including paralog-specific (vs UTX) action at Has2, enhancer-looping in neuroblastoma, glycolytic LDHA control, and CD8+ T cell priming.

    Evidence Paralog-specific knockdown with ChIP and HA assays; ATAC-seq and H3K4me1/H3K27me3 ChIP with genetic rescue in neuroblastoma; ChIP-seq/RNA-seq in osteosarcoma; ATAC-seq/H3K27me3 ChIP-seq/RNA-seq in T cells

    PMID:33664867 PMID:33730567 PMID:34893606 PMID:35926054

    Open questions at the time
    • Basis of JMJD3 vs UTX functional specialization unknown
    • How KDM6B influences H3K4me1 and CTCF/BORIS-dependent looping mechanistically unresolved
  10. 2022 Medium

    Consolidated KDM6B as a recruited partner across diverse tissues—TFDP1 in palatogenesis, Tau in neurons, Isl1-Lhx3 in motor neurons, and macrophage inflammatory programs—and linked it to DNA-repair-coupled cell death.

    Evidence Conditional KOs with ChIP, Co-IP, scRNA-seq, behavioral/synaptic readouts, and MGMT/PARP-1 DNA repair assays

    PMID:35177643 PMID:35212626 PMID:35443173 PMID:35648484 PMID:36028572 PMID:36127466

    Open questions at the time
    • Why paralog KDM6A cannot compensate in several contexts is unexplained
    • Direct versus indirect nature of the Tau interaction not fully resolved
  11. 2023 High

    Established KDM6B as a therapeutic target in tumor immunity, showing myeloid-specific deletion reprograms suppressive myeloid cells and sensitizes glioblastoma to checkpoint blockade.

    Evidence Myeloid-specific Kdm6b KO with GBM models, single-cell and spatial transcriptomics, pharmacological inhibition, and anti-PD1 combination in vivo

    PMID:37653141

    Open questions at the time
    • Direct KDM6B targets driving Mafb/Socs3/Sirpa suppression not pinpointed
    • Whether effects are demethylase-dependent not fully partitioned
  12. 2024 Medium

    Extended upstream regulation of KDM6B to microRNA control, showing miR-93-5p represses KDM6B translation while KDM6B activates BMP2 to drive odontogenic differentiation.

    Evidence Dual luciferase reporter, ChIP-qPCR at BMP2 promoter, and in vivo pulpotomy model

    PMID:38218880

    Open questions at the time
    • Broader miRNA regulatory network for KDM6B not mapped
    • Single-lab validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how KDM6B's catalytic and non-catalytic activities are selected and balanced at individual loci, and what structural features dictate its partner- and paralog-specific recruitment.
  • No structural model explaining partner-specific recruitment
  • Determinants of demethylase-dependent vs -independent gene activation undefined
  • Mechanism distinguishing KDM6B from KDM6A/UTX at shared loci unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2 GO:0016787 hydrolase activity 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CEBPBISL1KLF4NFKB1NIPBLPHF20SMAD2TRIM26

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 JMJD3 (KDM6B) catalyzes demethylation of tri-methylated H3K27 (H3K27me3). Ectopic expression of JMJD3 causes a strong decrease of H3K27me3 levels and delocalization of polycomb proteins in vivo. The C. elegans ortholog F18E9.5 is required for gonad development. In vitro demethylase assay, ectopic expression in cells with H3K27me3 immunostaining, C. elegans RNAi/mutation Nature High 17713478
2013 Jmjd3 inhibits somatic cell reprogramming through two distinct mechanisms: (1) a demethylase-dependent pathway upregulating the INK4a/Arf locus, and (2) a demethylase-independent pathway in which Jmjd3 recruits E3 ubiquitin ligase Trim26 to target PHF20 for ubiquitination and degradation. iPSC reprogramming assays in wild-type vs. Jmjd3-deficient MEFs, ectopic expression, Co-IP, ubiquitination assays, catalytically inactive mutant controls Cell High 23452852
2012 KDM6B promotes TGF-β-induced epithelial-mesenchymal transition (EMT) in mammary epithelial cells by demethylating H3K27me3 at the SNAI1 promoter, stimulating SNAI1 expression. KDM6B is induced by TGF-β and its knockdown inhibits EMT and breast cancer cell invasion. KDM6B knockdown and overexpression, ChIP assay for H3K27me3 at SNAI1 promoter, invasion assays The Journal of biological chemistry Medium 23152497
2012 KDM6B promotes RNA Polymerase II progression along gene bodies of TGF-β-responsive genes by demethylating H3K27me3 in intragenic regions, thereby facilitating transcriptional elongation rather than only initiation. ChIP-seq for JMJD3, elongating RNAPII (Ser2-phospho), and H3K27me3 upon TGF-β treatment; genome-wide analysis Molecular biology of the cell High 23243002
2013 Jmjd3 is required for mesoderm and subsequent cardiovascular lineage commitment in mouse embryonic stem cells. Jmjd3 reduces H3K27me3 marks at the Brachyury promoter and facilitates recruitment of β-catenin, which is critical for Wnt signal-induced mesoderm differentiation. Jmjd3 ablation in mouse ESCs, ChIP for H3K27me3 at Brachyury promoter, β-catenin recruitment assay Circulation research Medium 23856522
2013 KDM6B and EED (PRC2 component) coordinately regulate the first mammalian cell lineage commitment. The relative levels of EED and KDM6B determine PRC2 recruitment and H3K27me3 status at CDX2 and GATA3 chromatin domains, leading to their activation in trophectoderm (TE) and repression in inner cell mass (ICM). Ectopic EED gain plus KDM6B depletion abrogates CDX2/GATA3 expression in TE and causes failure of embryo implantation. Genetic manipulation in preimplantation mouse embryos, ChIP for H3K27me3 at CDX2/GATA3 loci, phenotypic analysis of implantation failure Molecular and cellular biology Medium 23671187
2014 JMJD3 physically interacts with the tumor suppressor p53 (interaction dependent on the p53 tetramerization domain). Following DNA damage, JMJD3 is recruited to p53-bound promoters and enhancer elements in a p53-dependent manner, as demonstrated by genome-wide JMJD3 mapping showing significant overlap with p53 binding sites. Co-immunoprecipitation, ChIP-seq genome-wide mapping of JMJD3 and p53, p53 expression-dependent recruitment assay after DNA damage PloS one Medium 24797517
2015 Jmjd3-catalyzed removal of H3K27me3 is required for brown adipose tissue (BAT)-selective gene expression and development of beige adipocytes. Jmjd3 is recruited in part through the transcription factor Rreb1. Gain- and loss-of-function Jmjd3 transgenic mice show age-dependent body weight changes and cold intolerance, respectively. H3K27me3 ChIP-seq in brown/white preadipocytes, Jmjd3 gain/loss-of-function in vitro and transgenic mice, Rreb1-mediated recruitment assay Developmental cell High 26625958
2016 JMJD3 physically interacts with NF-κB and cooperates with it to induce expression of inflammatory, matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at their promoters during keratinocyte wound healing. Inactivation of either JMJD3 or NF-κB impairs keratinocyte wound healing. Co-immunoprecipitation of JMJD3 and NF-κB, ChIP for H3K27me3 at target gene promoters, JMJD3/NF-κB inactivation in vitro and in vivo wound models The Journal of investigative dermatology Medium 26802933
2016 ISL1 physically interacts with JMJD3 and recruits it to enhancers of cardiac transcription factor genes (Myocd and Mef2c) to demethylate H3K27me3. ISL1 also modulates JMJD3's demethylase activity. Conditional depletion of JMJD3 impairs cardiac progenitor cell differentiation, phenocopying ISL1 depletion. Co-immunoprecipitation of ISL1 and JMJD3, ChIP for H3K27me3 at Myocd/Mef2c enhancers, conditional JMJD3 depletion in cardiac progenitors Nucleic acids research Medium 27105846
2017 KDM6B regulates multiple myeloma cell growth via a demethylase-independent mechanism: KDM6B is recruited to MAPK pathway gene loci (including ELK1 and FOS) and upregulates their expression without affecting H3K27 methylation levels. Overexpression of catalytically inactive KDM6B similarly activates MAPK pathway genes. KDM6B is regulated by NF-κB signaling in MM cells. shRNA knockdown, CRISPR KO, RNA-seq, ChIP-qPCR, overexpression of catalytically inactive KDM6B mutant, IKKβ inhibitor treatment Leukemia High 28487543
2017 JMJD3 and NF-κB activate Notch1 transcription in wounded keratinocytes by removing H3K27me3 at the Notch1 promoter. Notch1 in turn activates RhoU and PLAU, which regulate filopodia formation and cell migration for skin wound healing. ChIP for H3K27me3 at Notch1 promoter, JMJD3/NF-κB depletion, Notch1 depletion with migration/filopodia assays in vitro and in vivo wound models Scientific reports Medium 28747631
2018 JMJD3 forms a positive autoregulatory loop with SIRT1 and PPARα upon fasting-induced PKA signaling to epigenetically activate mitochondrial fatty acid β-oxidation genes (Fgf21, Cpt1a, Mcad) by removing H3K27me3. JMJD3 acts as a gene-specific transcriptional partner of SIRT1 selectively on β-oxidation genes but not gluconeogenic genes. Liver-specific knockdown of JMJD3 causes β-oxidation defects and hepatosteatosis. Co-immunoprecipitation of JMJD3/SIRT1/PPARα, ChIP for H3K27me3 at β-oxidation gene promoters, liver-specific JMJD3 knockdown, metabolic phenotyping The Journal of clinical investigation High 29911994
2018 JMJD3 promotes cardiac hypertrophy through a demethylase-dependent mechanism: JMJD3 is recruited to the β-MHC promoter, demethylates H3K27me3, and promotes β-MHC expression. Overexpression of wild-type but not demethylase-defective mutant JMJD3 promotes cardiomyocyte hypertrophy. Overexpression of WT vs. demethylase-defective JMJD3, ChIP for H3K27me3 at β-MHC promoter, isoproterenol-induced hypertrophy model, GSK-J4 inhibitor treatment Molecular and cellular endocrinology Medium 29753027
2018 JMJD3 promotes ABC-subtype DLBCL survival by demethylase-dependent upregulation of IRF4, which reciprocally stimulates JMJD3 expression, forming a positive feedback loop. JMJD3 silencing in DLBCL subtypes, IRF4 rescue experiments, demethylase activity-dependent assays, in vivo siRNA tumor treatment Oncotarget Medium 27102442
2018 JMJD3 facilitates myeloid differentiation of AML cells via a physical and functional association with transcription factor C/EBPβ. JMJD3 modulates H3K4 and H3K27 methylation levels to activate myelopoietic regulatory genes, exerting an oncorepressor effect in M2/M3 AML subtypes. RNA-seq, ChIP-PCR, co-immunoprecipitation of JMJD3 and C/EBPβ, JMJD3 overexpression/knockdown in AML cell lines Nature communications Medium 30135572
2019 JMJD3 regulates CD4+ T cell trafficking by activating Pdlim4 transcription through binding to the Pdlim4 promoter and gene body in cooperation with the zinc finger transcription factor KLF2. PDLIM4 acts as an adaptor between S1P1 and F-actin to enable T cell egress. JMJD3 deficiency leads to T cell accumulation in the thymus. Gene expression profiling and ChIP-seq in JMJD3-deficient CD4+ T cells, Co-IP of JMJD3 and KLF2, S1P1/F-actin interaction assays, in vivo T cell trafficking analysis The Journal of clinical investigation High 31393857
2019 KDM6B is required for hematopoietic stem cell (HSC) self-renewal under inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation state in HSCs due to increased expression of AP-1 complex (Fos/Jun) and IER genes independently of chromatin modifications. Targeting AP-1 restores Kdm6b-deficient HSC function. Conditional Kdm6b KO in mice, HSC functional assays, RNA-seq, AP-1 targeting rescue experiments Leukemia Medium 30936419
2020 JMJD3 is specifically recruited by KLF4 during reprogramming to reduce H3K27me3 at enhancers and promoters of epithelial and pluripotency genes. JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL, and drives transcriptional elongation. Simultaneously, JMJD3 induces Ink4a and degrades PHF20 (via Trim26) in a KLF4-independent manner. ChIP-seq for H3K27me3 and JMJD3 during reprogramming, Co-IP of JMJD3-KLF4 and JMJD3-NIPBL, enhancer-promoter looping analysis, Trim26-mediated PHF20 degradation assays Nature communications High 33033262
2020 STAT3 binds the Jmjd3 promoter and represses Jmjd3 transcription in glioblastoma stem cells. STAT3 inhibition upregulates JMJD3, which demethylates H3K27 at differentiation gene promoters (Myt1, FGF21, GDF15), slows glioblastoma stem cell growth, and Jmjd3 knockdown rescues STAT3 inhibitor-induced neurosphere formation defects. STAT3 ChIP at Jmjd3 promoter, JMJD3 overexpression/knockdown, H3K27 demethylation ChIP at differentiation gene promoters, neurosphere assays PloS one Medium 28384648
2020 In reptilian temperature-dependent sex determination, STAT3 phosphorylated at the female-producing temperature binds the Kdm6b locus and represses Kdm6b transcription, blocking the male developmental pathway. Ca2+ influx elevated at female temperature mediates STAT3 phosphorylation as a temperature-sensitive regulator. ChIP for pSTAT3 at Kdm6b locus, Ca2+ manipulation, STAT3 phosphorylation assays in turtle embryos at different temperatures Science Medium 32299951
2021 JMJD3 (but not UTX) removes H3K27me3 marks at the Has2 locus in muscle stem cells to initiate hyaluronic acid (HA) production. This JMJD3-driven HA synthesis establishes an extracellular matrix enabling MuSCs to exit quiescence and overcome inhibitory inflammation during muscle regeneration. JMJD3/UTX-specific knockdown in MuSCs, ChIP for H3K27me3 at Has2 locus, HA production assays, in vitro and in vivo muscle regeneration models Science High 35926054
2021 KDM6B promotes CDK4/6-pRB-E2F oncogenic pathway in MYCN-amplified neuroblastoma via H3K27me3-dependent enhancer-promoter interactions: KDM6B inhibition reduces H3K27me3 but also decreases the enhancer mark H3K4me1 at CTCF/BORIS binding sites, disrupting long-range chromatin interactions of MYCN and E2F targets. KDM6B inhibition with GSK-J4, ATAC-seq for chromatin accessibility, H3K27me3/H3K4me1 ChIP, CDK4/6 overexpression and Rb1 KO resistance experiments Nature communications High 34893606
2021 KDM6B mediates H3K27me3 demethylation at the LDHA promoter to upregulate LDHA expression in osteosarcoma cells, promoting aerobic glycolysis and lung metastasis. ChIP-seq and RNA-seq identified LDHA as a direct KDM6B target. ChIP-seq, RNA-seq, ChIP-qPCR for H3K27me3 at LDHA promoter, KDM6B knockdown with LDHA rescue, in vivo metastasis model Theranostics Medium 33664867
2021 In macrophages, interferon-β regulates Jmjd3 expression via the JAK/STAT pathway, and JMJD3 induces NF-κB-mediated inflammatory gene transcription by removing repressive H3K27me3 marks from inflammatory gene promoters. Myeloid-specific Jmjd3 deletion preserved H3K27me3 at inflammatory gene promoters and reduced AAA expansion. Myeloid-specific Jmjd3 KO mice (Jmjd3f/fLyz2Cre+), single-cell RNA-seq of human AAA tissue, H3K27me3 ChIP at inflammatory gene promoters, pharmacological inhibition in elastase/angiotensin II AAA models The Journal of experimental medicine High 33779682
2021 KDM6B demethylates H3K27me3 at the cyclin D1 promoter and cooperates with Smad2/3 to promote cyclin D1 transcription in prostate cancer. Androgen receptor decreases KDM6B transcription, placing KDM6B downstream of androgen signaling. ChIP for H3K27me3 at cyclin D1 promoter, KDM6B overexpression/knockdown, Co-IP of KDM6B and Smad2/3, AR-KDM6B transcriptional regulation assay, in vivo xenograft models Cell death & disease Medium 33414463
2021 KDM6B is recruited to the KDM6B locus by the SMAD2/3 complex downstream of activin A signaling in hippocampal neurons. Activin A treatment induces KDM6B expression via SMAD2/3 binding at the Kdm6b gene, conserved in human forebrain neurons. ChIP experiments with hippocampal lysates for SMAD2/3 binding at Kdm6b gene after electroconvulsive seizures, human ESC-derived forebrain neuron validation Molecular neurobiology Medium 26215835
2021 KDM6B-dependent H3K27me3 demethylation is required for early CD8+ T cell differentiation: KDM6B is rapidly upregulated prior to the first cell division after naive T cell activation, enabling H3K27me3 removal at differentiation/proliferation genes. KDM6B inhibition limits the magnitude of primary virus-specific CD8+ T cell responses and memory formation. Genome-wide ATAC-seq, H3K27me3 ChIP-seq, RNA-seq, KDM6B inhibition during virus-specific T cell responses in vivo Cell reports High 33730567
2022 KDM6B interacts with transcription factor TFDP1 to activate Trp53 expression during palatogenesis. Without KDM6B, TFDP1 cannot activate Trp53. Activity of H3K27me3 at the Trp53 promoter is antagonistically controlled by KDM6B and EZH2. KDM6A cannot compensate for KDM6B loss in this context. Conditional Kdm6b KO in cranial neural crest cells, ChIP for H3K27me3 at Trp53 promoter, Co-IP/interaction assays of KDM6B and TFDP1, rescue experiments with Kdm6a eLife Medium 35212626
2022 KDM6B cooperates with Tau to regulate synaptic plasticity and cognition. Tau interacts with KDM6B and recruits it to the promoters of Slc17a7 (VGLUT1) and Slc17a6 (VGLUT2) in neurons, reducing local H3K27me3 and inducing VGLUT1/2 expression. Conditional KDM6B KO in excitatory neurons reduces spine density and impairs memory. Conditional KO in excitatory neurons, ChIP for H3K27me3 at VGLUT1/2 promoters, Co-IP of KDM6B and Tau, spine density/synaptic activity measurements, Tau KO loss-of-function rescue Molecular psychiatry Medium 36028572
2022 KDM6B promotes PARthanatos (PARP-1-dependent cell death) in response to alkylating agents by suppressing MGMT expression: KDM6B knockout reduces H3K27me3 at the MGMT promoter, enhancing MGMT expression and direct DNA repair, thereby inhibiting PARP-1 hyperactivation. KDM6B KO also triggers sustained Chk1 phosphorylation activating a secondary XRCC1-dependent repair pathway. KDM6B KO, ChIP for H3K27me3 at MGMT promoter, PARP-1 hyperactivation assays, MGMT expression and DNA repair functional assays, Chk1 phosphorylation analysis Nucleic acids research Medium 35648484
2022 Kdm6b regulates motor neuron subtype diversification by working together with the transcription factor complex Isl1-Lhx3. Kdm6b promotes MMC and HMC fates while inhibiting LMC and PGC identities in mouse embryonic spinal cord. Single-cell RNA-seq demonstrated cell-type heterogeneity dependent on Kdm6b. Conditional Kdm6b KO in mouse embryonic motor neurons, single-cell RNA-seq, Isl1-Lhx3 complex interaction studies, motor column fate analysis Nature communications Medium 35177643
2022 In the context of diabetic wound healing, IL-6 activates the JAK1,3/STAT3 pathway to regulate JMJD3 expression in diabetic wound macrophages. Late-elevated JMJD3 induces NFκB-mediated inflammatory transcription via H3K27me3 removal. JMJD3 also controls STING (Tmem173) gene expression in wound macrophages through an H3K27me3 mechanism. Myeloid-specific Jmjd3 KO mice, single-cell RNA-seq, RNA-seq of isolated wound macrophages, H3K27me3 ChIP, nanoparticle-mediated JMJD3 inhibition in diabetic wounds Cellular & molecular immunology Medium 36127466
2022 IFNβ reduces the cellular α-ketoglutarate/succinate ratio by inhibiting isocitrate dehydrogenase and boosting succinate, which potently blocks the JMJD3-IRF4-dependent M2 macrophage polarization pathway. Supplementation with α-ketoglutarate reverses IFNβ-mediated suppression of JMJD3-IRF4 responses. Metabolic flux analysis (isotope tracing), α-ketoglutarate supplementation rescue, macrophage polarization assays, JMJD3-IRF4 pathway functional studies Cell reports Medium 35443173
2023 Myeloid-specific Kdm6b deletion enhances antigen presentation, interferon response, and phagocytosis in myeloid cells by inhibiting mediators of immune suppression including Mafb, Socs3, and Sirpa. This reprogramming sensitizes glioblastoma to anti-PD1 immunotherapy. Pharmacological KDM6B inhibition mirrors the genetic Kdm6b deletion phenotype. Myeloid-specific Kdm6b KO mice with GBM tumor model, single-cell and spatial transcriptomics, mechanistic gene expression studies, anti-PD1 combination treatment in vivo Nature cancer High 37653141
2021 The lncRNA DNM3OS physically interacts with KDM6B in the nucleus of HCC cells. This DNM3OS-KDM6B association reduces H3K27me3 at the TIAM1 promoter, inducing TIAM1 expression and promoting HCC metastasis. Nuclear localization and pulldown of DNM3OS-KDM6B interaction, ChIP for H3K27me3 at TIAM1 promoter, TIAM1 rescue experiments Cancer letters Low 33472090
2021 KDM6B functions as a coactivator of HIF-1α-mediated Nox4 transactivation in response to intermittent hypoxia (IH). KDM6B protein and enzyme activity are increased by IH independently of HIF-1α. KDM6B blockade abolishes HIF-1α binding to the Nox4 HRE promoter and prevents IH-induced hypertension in vivo. ChIP for HIF-1α binding at Nox4 HRE, KDM6B shRNA and pharmacological inhibition (GSKJ4), KDM6B enzyme activity assay, rat IH hypertension model Physiological genomics Medium 34297635
2017 Conditional deletion of Kdm6b (using Col2a1-CreER) in chondrocytes causes skeletal abnormalities and accelerated osteoarthritis via inhibition of chondrocyte anabolic gene expression. RNA-seq identified downregulation of anabolic chondrocyte genes in Kdm6b-deficient chondrocytes. Conditional Kdm6b KO in cartilage (Col2a1-CreER), RNA-seq, intra-articular shRNA lentiviral injection, OA histological scoring Annals of the rheumatic diseases Medium 28314754
2011 KDM6B (JMJD3) expression is induced by the EBV oncogene LMP1 in germinal centre B cells. KDM6B depletion restores H3K27me3 trimethylation on KDM6B target genes in Hodgkin's lymphoma cells. LMP1 ectopic expression, KDM6B depletion, ChIP for H3K27me3 at KDM6B target gene loci Oncogene Medium 21242977
2011 JMJD3 expression is induced by 1,25(OH)2D3 in a VDR-dependent manner (abolished by cycloheximide, requiring new protein synthesis). JMJD3 modulates vitamin D receptor target gene expression; knockdown of JMJD3 or expression of an inactive mutant JMJD3 reduces 1,25(OH)2D3-induced gene activation and epithelial phenotype, and upregulates EMT inducers. JMJD3 promoter activation assays, VDR-dependent expression analysis, JMJD3 knockdown and inactive mutant expression, ChIP for H3K27me3 at VDR target gene promoters Human molecular genetics Medium 21890490
2019 KDM6B demethylates H3K27me3 at neuronal gene promoters to activate transcription during neuroblastoma differentiation. KDM6B expression is upregulated by retinoic acid via HOXC9. KDM6B physically interacts with HOXC9 to target neuronal genes for epigenetic activation, and is required for HOXC9-induced differentiation. ChIP for H3K27me3 at neuronal gene promoters, KDM6B overexpression/depletion, Co-IP of KDM6B and HOXC9, retinoic acid treatment Oncogenesis Medium 30631055
2024 miR-93-5p targets the 3' UTR of KDM6B to inhibit its protein translation. KDM6B binds the BMP2 promoter and demethylates H3K27me3 marks to activate BMP2 transcription in dental pulp stem cells, promoting odontogenic differentiation and tertiary dentin formation. Dual luciferase reporter assay for miR-93-5p/KDM6B 3'UTR, ChIP-qPCR for KDM6B binding and H3K27me3 at BMP2 promoter, KDM6B overexpression in rat pulpotomy model Journal of translational medicine Medium 38218880

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 1094 17713478
2012 Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs. Cell stem cell 286 22770241
2012 Histone demethylase KDM6B promotes epithelial-mesenchymal transition. The Journal of biological chemistry 143 23152497
2021 Cancer-derived exosomal miR-138-5p modulates polarization of tumor-associated macrophages through inhibition of KDM6B. Theranostics 138 34093857
2011 KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells. Human molecular genetics 137 21890490
2013 Jmjd3 inhibits reprogramming by upregulating expression of INK4a/Arf and targeting PHF20 for ubiquitination. Cell 129 23452852
2021 Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms. The Journal of experimental medicine 122 33779682
2015 JMJD3 as an epigenetic regulator in development and disease. The international journal of biochemistry & cell biology 121 26193001
2022 Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair. Cellular & molecular immunology 117 36127466
2014 Histone demethylase Jumonji D3 (JMJD3/KDM6B) at the nexus of epigenetic regulation of inflammation and the aging process. Journal of molecular medicine (Berlin, Germany) 117 24925089
2011 The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma. Oncogene 116 21242977
2020 Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b. Science (New York, N.Y.) 112 32299951
2019 JMJD3 in the regulation of human diseases. Protein & cell 104 31701394
2021 Histone H3K27 methyltransferase EZH2 and demethylase JMJD3 regulate hepatic stellate cells activation and liver fibrosis. Theranostics 98 33391480
2021 Exosomal microRNA-22-3p alleviates cerebral ischemic injury by modulating KDM6B/BMP2/BMF axis. Stem cell research & therapy 87 33546766
2018 Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for acute myeloid leukemia. Journal of cancer research and clinical oncology 83 29594337
2016 Histone H3K27 Demethylase JMJD3 in Cooperation with NF-κB Regulates Keratinocyte Wound Healing. The Journal of investigative dermatology 82 26802933
2016 Histone demethylases in physiology and cancer: a tale of two enzymes, JMJD3 and UTX. Current opinion in genetics & development 81 27151432
2015 Jmjd3-Mediated H3K27me3 Dynamics Orchestrate Brown Fat Development and Regulate White Fat Plasticity. Developmental cell 79 26625958
2014 The histone lysine demethylase JMJD3/KDM6B is recruited to p53 bound promoters and enhancer elements in a p53 dependent manner. PloS one 75 24797517
2018 Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fatty acid β-oxidation. The Journal of clinical investigation 74 29911994
2021 KDM6B-mediated histone demethylation of LDHA promotes lung metastasis of osteosarcoma. Theranostics 73 33664867
2016 Aberrant JMJD3 Expression Upregulates Slug to Promote Migration, Invasion, and Stem Cell-Like Behaviors in Hepatocellular Carcinoma. Cancer research 73 27651311
2017 KDM6B modulates MAPK pathway mediating multiple myeloma cell growth and survival. Leukemia 68 28487543
2022 JMJD3 activated hyaluronan synthesis drives muscle regeneration in an inflammatory environment. Science (New York, N.Y.) 67 35926054
2013 Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells. Circulation research 66 23856522
2017 Kdm6b regulates cartilage development and homeostasis through anabolic metabolism. Annals of the rheumatic diseases 61 28314754
2016 Inhibition of demethylase KDM6B sensitizes diffuse large B-cell lymphoma to chemotherapeutic drugs. Haematologica 61 27742770
2020 JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells. Nature communications 60 31959746
2018 Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune response in rheumatoid arthritis. Cellular & molecular immunology 57 29844591
2022 Type I interferon antagonism of the JMJD3-IRF4 pathway modulates macrophage activation and polarization. Cell reports 53 35443173
2017 Regulation of the JMJD3 (KDM6B) histone demethylase in glioblastoma stem cells by STAT3. PloS one 53 28384648
2019 Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis. Leukemia 52 30936419
2019 The role and prospect of JMJD3 in stem cells and cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 52 31545292
2018 JMJD3 facilitates C/EBPβ-centered transcriptional program to exert oncorepressor activity in AML. Nature communications 52 30135572
2017 JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing. Scientific reports 51 28747631
2021 SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade. Nature communications 49 34262032
2023 Jumonji domain-containing protein-3 (JMJD3) promotes myeloid fibroblast activation and macrophage polarization in kidney fibrosis. British journal of pharmacology 48 37076137
2012 RNA polymerase II progression through H3K27me3-enriched gene bodies requires JMJD3 histone demethylase. Molecular biology of the cell 48 23243002
2020 Jmjd3 regulates inflammasome activation and aggravates DSS-induced colitis in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 47 31971317
2013 EED and KDM6B coordinate the first mammalian cell lineage commitment to ensure embryo implantation. Molecular and cellular biology 47 23671187
2021 KDM6B is an androgen regulated gene and plays oncogenic roles by demethylating H3K27me3 at cyclin D1 promoter in prostate cancer. Cell death & disease 43 33414463
2012 Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line. Cell biochemistry and function 43 22252741
2020 JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma. Cell death & disease 42 33318475
2021 KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma. Nature communications 41 34893606
2018 KDM6B Counteracts EZH2-Mediated Suppression of IGFBP5 to Confer Resistance to PI3K/AKT Inhibitor Treatment in Breast Cancer. Molecular cancer therapeutics 41 29925528
2022 The ERα/KDM6B regulatory axis modulates osteogenic differentiation in human mesenchymal stem cells. Bone research 40 34992221
2014 MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells. FEBS letters 39 24726732
2016 ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells. Nucleic acids research 38 27105846
2021 KDM6B (JMJD3) and its dual role in cancer. Biochimie 37 33581195
2015 KDM6B induces epithelial-mesenchymal transition and enhances clear cell renal cell carcinoma metastasis through the activation of SLUG. International journal of clinical and experimental pathology 37 26261509
2023 Myeloid-specific KDM6B inhibition sensitizes glioblastoma to PD1 blockade. Nature cancer 36 37653141
2021 JMJD3: a critical epigenetic regulator in stem cell fate. Cell communication and signaling : CCS 36 34217316
2020 JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency. Nature communications 36 33033262
2019 Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features. American journal of medical genetics. Part A 36 31124279
2018 JMJD3 inhibition protects against isoproterenol-induced cardiac hypertrophy by suppressing β-MHC expression. Molecular and cellular endocrinology 36 29753027
2022 Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1. International journal of oral science 35 35831280
2021 Epigenetic regulation of TGF-β-induced EMT by JMJD3/KDM6B histone H3K27 demethylase. Oncogenesis 35 33637682
2018 KDM6B overexpression activates innate immune signaling and impairs hematopoiesis in mice. Blood advances 34 30275007
2018 KDM6B promotes ovarian cancer cell migration and invasion by induced transforming growth factor-β1 expression. Journal of cellular biochemistry 34 30277596
2021 KDM6B epigenetically regulated-interleukin-6 expression in the dorsal root ganglia and spinal dorsal horn contributes to the development and maintenance of neuropathic pain following peripheral nerve injury in male rats. Brain, behavior, and immunity 30 34464689
2019 Histone demethylase KDM6B has an anti-tumorigenic function in neuroblastoma by promoting differentiation. Oncogenesis 30 30631055
2017 Histone demethylases UTX and JMJD3 are required for NKT cell development in mice. Cell & bioscience 29 28529687
2016 Histone demethylase JMJD3 at the intersection of cellular senescence and cancer. Biochimica et biophysica acta 29 26957416
2018 Inhibiting Jumoji domain containing protein 3 (JMJD3) prevent neuronal apoptosis from stroke. Experimental neurology 28 30028997
2022 Jmjd3/IRF4 axis aggravates myeloid fibroblast activation and m2 macrophage to myofibroblast transition in renal fibrosis. Frontiers in immunology 27 36159833
2021 Tumor-associated mesenchymal stem cells promote hepatocellular carcinoma metastasis via a DNM3OS/KDM6B/TIAM1 axis. Cancer letters 27 33472090
2020 Histone Demethylase JMJD3 Mediated Doxorubicin-Induced Cardiomyopathy by Suppressing SESN2 Expression. Frontiers in cell and developmental biology 27 33117796
2018 Myeloid Kdm6b deficiency results in advanced atherosclerosis. Atherosclerosis 27 29908485
2021 Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression. Scientific reports 26 33479437
2019 EZH2, JMJD3, and UTX epigenetically regulate hepatic plasticity inducing retro-differentiation and proliferation of liver cells. Cell death & disease 26 31285428
2016 JMJD3 promotes survival of diffuse large B-cell lymphoma subtypes via distinct mechanisms. Oncotarget 26 27102442
2015 KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 26303949
2020 Targeting JMJD3 histone demethylase mediates cardiac fibrosis and cardiac function following myocardial infarction. Biochemical and biophysical research communications 25 32513540
2021 KDM6B-dependent chromatin remodeling underpins effective virus-specific CD8+ T cell differentiation. Cell reports 24 33730567
2023 The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder. American journal of human genetics 23 37196654
2022 KDM6B cooperates with Tau and regulates synaptic plasticity and cognition via inducing VGLUT1/2. Molecular psychiatry 22 36028572
2021 The Functions of the Demethylase JMJD3 in Cancer. International journal of molecular sciences 22 33478063
2021 KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPβ transcription. BMC cancer 21 34001062
2022 The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development. Nature communications 20 35177643
2022 KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression. Cell death & disease 20 36564369
2015 Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A Signaling. Molecular neurobiology 20 26215835
2021 Allyl sulfide promotes osteoblast differentiation and bone density via reducing mitochondrial DNA release mediated Kdm6b/H3K27me3 epigenetic mechanism. Biochemical and biophysical research communications 19 33556823
2024 Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer. Clinical epigenetics 17 38576048
2024 Curcumenol regulates Histone H3K27me3 demethylases KDM6B affecting Succinic acid metabolism to alleviate cartilage degeneration in knee osteoarthritis. Phytomedicine : international journal of phytotherapy and phytopharmacology 17 39126921
2022 KDM6B interacts with TFDP1 to activate P53 signaling in regulating mouse palatogenesis. eLife 17 35212626
2022 The JMJD3 histone demethylase inhibitor GSK-J1 ameliorates lipopolysaccharide-induced inflammation in a mastitis model. The Journal of biological chemistry 17 35526564
2021 Lysine demethylase KDM6B regulates HIF-1α-mediated systemic and cellular responses to intermittent hypoxia. Physiological genomics 17 34297635
2019 JMJD3 regulates CD4 T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4. The Journal of clinical investigation 17 31393857
2022 KDM6B promotes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response. Nucleic acids research 16 35648484
2022 JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis. International immunopharmacology 16 35777266
2020 Sodium lactate promotes stemness of human mesenchymal stem cells through KDM6B mediated glycolytic metabolism. Biochemical and biophysical research communications 16 32891432
2018 Epigenetic Regulation of EMT (Epithelial to Mesenchymal Transition) and Tumor Aggressiveness: A View on Paradoxical Roles of KDM6B and EZH2. Epigenomes 16 34991274
2017 The Roles of Histone Demethylase Jmjd3 in Osteoblast Differentiation and Apoptosis. Journal of clinical medicine 16 28241471
2016 The Roles of Histone Demethylase UTX and JMJD3 (KDM6B) in Cancers: Current Progress and Future Perspectives. Current medicinal chemistry 16 27458035
2012 Tetrahymena thermophila JMJD3 homolog regulates H3K27 methylation and nuclear differentiation. Eukaryotic cell 16 22427430
2024 AGEs impair osteogenesis in orthodontic force-induced periodontal ligament stem cells through the KDM6B/Wnt self-reinforcing loop. Stem cell research & therapy 15 39548506
2024 MicroRNA-93-5p regulates odontogenic differentiation and dentin formation via KDM6B. Journal of translational medicine 14 38218880
2024 Diabetic Wound Keratinocytes Induce Macrophage JMJD3-Mediated Nlrp3 Expression via IL-1R Signaling. Diabetes 14 38869447
2022 Kdm6b Haploinsufficiency Causes ASD/ADHD-Like Behavioral Deficits in Mice. Frontiers in behavioral neuroscience 14 35711692

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