Affinage

KDM4D

Lysine-specific demethylase 4D · UniProt Q6B0I6

Length
523 aa
Mass
58.6 kDa
Annotated
2026-06-10
46 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM4D (JMJD2D) is a JmjC-domain histone demethylase that primarily removes di- and tri-methyl marks from H3K9 to establish a transcriptionally permissive chromatin state at target loci, functioning broadly as a transcriptional coactivator across development, immunity, DNA repair, and cancer (PMID:25378304, PMID:30472235). Its stable chromatin association is gated by RNA: two non-canonical RNA-binding domains, with the N-terminal region (aa 115–236) required for chromatin association and subsequent H3K9me3 demethylation in cells (PMID:25378304). In addition to histone catalysis, KDM4D is recruited rapidly to DNA double-strand breaks through its C-terminal region in a PARP1-dependent manner, where it is ADP-ribosylated, binds poly(ADP-ribose), and is required for ATM-dependent signaling and Rad51/53BP1 focus formation during homology-directed repair and NHEJ (PMID:24550317, PMID:25714495). It also reduces H3K9me3 at replication origins, interacting with pre-RC components ORC and MCM and enabling Cdc45, PCNA, and polymerase δ recruitment to license pre-initiation complex assembly (PMID:27679476). As a coactivator KDM4D partners with numerous transcription factors—β-catenin/TCF4 and Notch (NICD), Gli2, HIF1α/HIF1β, STAT3-IRF1 and SP-1, NFIB/MLL1, and NF-κB—to demethylate H3K9me3 at their target promoters and drive programs in colorectal and liver cancer, angiogenesis, adipogenesis, and antiviral/innate immune signaling (PMID:30472235, PMID:32094404, PMID:32989255, PMID:32080306, PMID:35027670, PMID:42072725). Conversely, it antagonizes p53 in a demethylase-independent manner by blocking p53 recruitment to the p21 and PUMA promoters (PMID:32754284). KDM4D protein abundance is set by a ubiquitin-autophagy axis: TRIM14 recruits the deubiquitinases USP14 and BRCC3 to cleave K63-linked ubiquitin chains and prevent OPTN-mediated selective autophagic degradation, while SET7/9 methylates KDM4D at K427 to potentiate tumorigenesis (PMID:35145029, PMID:38045004, PMID:40088847). Genetically, Kdm4d-deficient male mice are subfertile owing to impaired sperm motility linked to altered H3K9me3 distribution in round spermatids (PMID:39034148).

Mechanistic history

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

    Established KDM4D as a catalytically dependent transcriptional coactivator by linking it to a nuclear receptor, defining its activating role on chromatin.

    Evidence Co-IP, domain mapping, and luciferase reporter assays with ligand-bound androgen receptor

    PMID:17555712

    Open questions at the time
    • No genome-wide AR target validation
    • Did not resolve which H3K9 methyl state is removed at AR loci
  2. 2012 Medium

    Showed KDM4D physically engages the p53 DNA-binding domain and can synergize at the p21 promoter, opening the question of whether KDM4D is a p53 activator or antagonist.

    Evidence Co-IP, in vitro binding, and luciferase reporter assays in overexpression

    PMID:22514644

    Open questions at the time
    • Catalytic-dependence vs independence of the p53 effect unresolved here
    • Overexpression-based; physiological context not tested
  3. 2014 High

    Defined a chromatin-independent DNA-repair function, placing KDM4D in the PARP1-ADP-ribosylation damage-response pathway upstream of ATM activation and repair focus formation.

    Evidence Live-cell imaging at laser-induced breaks, PARP1 inhibition, siRNA, immunofluorescence, DSB repair assays

    PMID:24550317

    Open questions at the time
    • Whether demethylase activity is needed at break sites not fully separated
    • Direct ADP-ribose acceptor residues not mapped
  4. 2014 High

    Revealed that RNA binding via two non-canonical domains is a prerequisite for KDM4D chromatin association, redefining how the enzyme is targeted to substrate.

    Evidence RNA-binding assays, domain mapping with mutagenesis, chromatin fractionation, H3K9me3 immunofluorescence

    PMID:25378304

    Open questions at the time
    • Identity of the bound RNA(s) not determined
    • Structural basis of non-canonical RNA recognition unknown
  5. 2015 Medium

    Connected the RNA-binding requirement to damage recruitment by showing PAR binding through the C-terminus and RNA dependence for accumulation at breaks.

    Evidence In vitro PAR-binding assay and laser micro-irradiation with RNA-binding-domain mutants

    PMID:25714495

    Open questions at the time
    • In vitro PAR binding not validated as direct in cells
    • Single-lab follow-up of the prior study
  6. 2016 High

    Extended KDM4D function to DNA replication, showing H3K9me3 removal at origins licenses pre-initiation complex assembly downstream of ORC/MCM.

    Evidence siRNA, ChIP, Co-IP, H3K9M histone-mutant rescue, replication assays

    PMID:27679476

    Open questions at the time
    • How KDM4D is recruited to specific origins not defined
    • Cell-cycle timing of activity not resolved
  7. 2017 Low

    Tested the substrate boundary of KDM4D, raising H3K79me3 as a possible additional substrate beyond H3K9.

    Evidence Total chemical synthesis of H3K79me3 and in vitro demethylase assay

    PMID:28434780

    Open questions at the time
    • In vitro only with no cellular validation
    • Described as 'potential' activity
  8. 2018 High

    Defined KDM4D as a coactivator for oncogenic transcription factors (β-catenin, HIF1β, NF-κB) that demethylates H3K9me3 at their targets to drive cancer and fibrogenic programs.

    Evidence Co-IP, ChIP, reporter assays, shRNA, xenograft and genetic mouse models across CRC, GIST, and liver fibrosis

    PMID:30060750 PMID:30472235 PMID:30527625

    Open questions at the time
    • Whether factor recruitment depends on KDM4D or vice versa varies by context
    • Direct vs indirect promoter targeting not always separated
  9. 2020 High

    Distinguished catalytic from non-catalytic functions, establishing KDM4D as a demethylase-independent p53 antagonist while also coactivating Gli2, HIF1, and β-catenin/Notch-driven stemness.

    Evidence Co-IP, ChIP, EMSA, catalytic-dead mutants, and KO mouse cancer models

    PMID:32080306 PMID:32094404 PMID:32754284 PMID:32989255 PMID:33434575

    Open questions at the time
    • Structural basis for p53-recruitment blockade not defined
    • How catalytic vs non-catalytic modes are selected at different loci unclear
  10. 2021 High

    Identified the post-translational control of KDM4D abundance, defining a TRIM14–USP14/BRCC3 deubiquitination axis that protects it from OPTN-mediated autophagy and a SET7/9 K427-methylation mark, plus its first crystal structures.

    Evidence Co-IP, ubiquitination assays, autophagy modulation, KO dendritic-cell and inflammation models, in vitro methylation, X-ray crystallography

    PMID:33780862 PMID:34017391 PMID:34820329 PMID:35145029 PMID:38045004

    Open questions at the time
    • Ubiquitin ligase placing the K63 chains not identified
    • How K427 methylation alters catalysis or interactions mechanistically unresolved
  11. 2023 Medium

    Broadened KDM4D into innate immunity and interferon biology, showing enhancer-associated localization, redistribution to inducible promoters, and cooperation with NF-κB/STAT3 to boost antiviral genes.

    Evidence ChIP-seq, eRNA assays, knockdown/overexpression in MEFs, Co-IP, and KO mouse viral infection models

    PMID:37275914 PMID:37701334 PMID:42072725

    Open questions at the time
    • How KDM4D enhancer pre-positioning is established not defined
    • Context-specific antiviral vs proviral (HBx-stabilizing) roles not reconciled
  12. 2024 Medium

    Demonstrated physiological and metabolic roles of KDM4D demethylase activity, including iron-sensitive control of stem-cell activation, RPS5-coupled differentiation, STAT3-IL-17F immunity, and a genetic requirement for sperm motility.

    Evidence ChIP, pathway rescue, mitochondrial assays, KO mouse models (infection, fertility), and structural drug-design crystallography

    PMID:38905308 PMID:38981336 PMID:39034148 PMID:39158700 PMID:40088847 PMID:41546606

    Open questions at the time
    • Mechanism coupling iron status to KDM4D activity not biochemically defined
    • Stage-specific spermatid targets of KDM4D not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which specific RNAs target KDM4D to chromatin and how this RNA-gated recruitment integrates with PAR binding, transcription-factor partnering, and the choice between catalytic and demethylase-independent modes at any given locus.
  • No identified physiological RNA ligand
  • No unifying model for locus-specific recruitment
  • Determinants of catalytic vs non-catalytic engagement unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 4 GO:0003723 RNA binding 2 GO:0016491 oxidoreductase activity 2 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-73894 DNA Repair 2 R-HSA-69306 DNA Replication 1
Partners
CTNNB1GLI2HIF1APARP1RPS5STAT3TP53TRIM14

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 KDM4D (JMJD2D) forms a complex with ligand-bound androgen receptor (AR) via its C-terminus, and overexpression of KDM4D stimulates AR transcriptional function in a catalytic activity-dependent manner, identifying it as an AR coactivator. Co-immunoprecipitation, domain mapping, luciferase reporter assay, overexpression/knockdown Biochemical and biophysical research communications Medium 17555712
2012 KDM4D (JMJD2D) forms a complex with p53 tumor suppressor, interacting with p53's DNA binding domain, and synergistically activates p21 promoter-driven transcription in a catalytic activity-dependent manner. Co-immunoprecipitation, in vitro binding assay, luciferase reporter assay, overexpression PloS one Medium 22514644
2014 KDM4D is rapidly recruited to DNA damage sites via its C-terminal region in a PARP1-dependent (but ATM-independent) manner; PARP1 ADP-ribosylates KDM4D after damage, and KDM4D is required for efficient ATM substrate phosphorylation, chromatin association of ATM, Rad51 and 53BP1 foci formation, and integrity of homology-directed repair and NHEJ. Live-cell imaging at laser-induced DNA damage sites, PARP1 inhibition, siRNA knockdown, immunofluorescence, DSB repair assays Proceedings of the National Academy of Sciences of the United States of America High 24550317
2014 KDM4D binds RNA independently of its demethylase activity via two non-canonical RNA binding domains (N-terminal aa 115–236 and C-terminal aa 348–523); RNA interaction with the N-terminal region is required for KDM4D chromatin association and subsequent H3K9me3 demethylation in cells. RNA binding assays, domain mapping, chromatin fractionation, H3K9me3 immunofluorescence upon RNA binding domain mutations Nucleic acids research High 25378304
2015 KDM4D binds poly(ADP-ribose) (PAR) in vitro via its C-terminal region, and KDM4D-RNA interaction is required for KDM4D accumulation at DNA breakage sites. PAR binding assay in vitro, laser micro-irradiation/live-cell imaging with RNA-binding domain mutants Cell cycle (Georgetown, Tex.) Medium 25714495
2016 KDM4D regulates DNA replication by reducing H3K9me3 at replication origins; it interacts with replication proteins ORC and MCM (pre-RC components) and its depletion impairs recruitment of Cdc45, PCNA, and polymerase δ (but not ORC/MCM) to origins, blocking pre-initiation complex formation. siRNA knockdown, chromatin immunoprecipitation, co-immunoprecipitation, rescue with H3K9M histone mutant, DNA replication assays Nucleic acids research High 27679476
2017 Chemical synthesis of trimethylated H3K79 enabled identification of KDM4D as a potential demethylase of H3K79me3 in vitro, extending its known substrate repertoire beyond H3K9. Total chemical protein synthesis of H3K79me3, in vitro demethylase assay Bioorganic & medicinal chemistry Low 28434780
2018 KDM4D (JMJD2D) physically interacts with β-catenin and demethylates H3K9me3 at promoters of β-catenin target genes (MYC, CCND1, MMP2, MMP9), activating their transcription and promoting colorectal cancer cell proliferation. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assay, shRNA knockdown, xenograft mouse model, Apcmin/+ and JMJD2D-KO mouse crosses Gastroenterology High 30472235
2018 KDM4D transcriptionally activates HIF1β expression by demethylating H3K9me3 and H3K36me3 at the HIF1β promoter, thereby promoting VEGFA-driven tumor angiogenesis and GIST progression. ChIP assay, luciferase reporter assay, Co-IP, shRNA knockdown, xenograft model Molecular cancer Medium 30060750
2018 KDM4D promotes TLR4 transcription in hepatic stellate cells by catalyzing H3K9 di- and tri-demethylation at the TLR4 promoter, activating TLR4/NF-κB signaling and contributing to liver fibrogenesis. ChIP assay, shRNA knockdown, transcriptome analysis, CCl4 mouse model, primary HSC culture EBioMedicine Medium 30527625
2020 KDM4D (JMJD2D) promotes Hedgehog target gene expression by interacting with Gli2 and reducing H3K9me3 levels at Hedgehog target gene promoters. Co-immunoprecipitation, chromatin immunoprecipitation, shRNA knockdown, DSS colitis mouse model, JMJD2D-KO mice Oncogene Medium 32094404
2020 KDM4D activates HIF1 signaling through three demethylase-activity-dependent mechanisms: (1) cooperating with SOX9 to enhance mTOR expression and promote HIF1α translation; (2) cooperating with c-Fos to enhance HIF1β transcription; (3) interacting and cooperating with HIF1α to enhance glycolytic gene expression. Co-immunoprecipitation, ChIP, shRNA knockdown, overexpression of demethylase-dead mutant, rescue experiments, xenograft model Oncogene Medium 32989255
2020 KDM4D (JMJD2D) directly interacts with p53 and inhibits p53 recruitment to the p21 and PUMA promoters in a demethylation activity-independent manner, antagonizing p53 tumor suppressor function in liver cancer cells. Co-immunoprecipitation, chromatin immunoprecipitation, electrophoretic mobility shift assay (EMSA), shRNA knockdown, DEN-induced liver cancer mouse model in KO mice Theranostics High 32754284
2020 KDM4D promotes liver cancer stem-like cell self-renewal by reducing H3K9me3 at EpCAM and Sox9 promoters via interaction with β-catenin/TCF4 and Notch1 intracellular domain (NICD), respectively. Co-immunoprecipitation, ChIP, shRNA knockdown, sphere formation assay, xenograft and lung metastasis models The Journal of biological chemistry Medium 33434575
2020 KDM4D cooperates with NFIB and MLL1 complex to regulate adipogenesis; KDM4D demethylation of H3K9me3 is required for NFIB and MLL1 to deposit H3K4me3 and activate PPARγ and C/EBPα expression at bivalent chromatin domains, but KDM4D is dispensable for NFIB/MLL1 binding to target promoters. Co-immunoprecipitation, ChIP, shRNA knockdown, overexpression rescue, adipogenic differentiation assay in C3H10T1/2 cells Scientific reports Medium 32080306
2021 TRIM14 recruits deubiquitinases USP14 and BRCC3 to cleave K63-linked ubiquitin chains on KDM4D, preventing optineurin (OPTN)-mediated selective autophagic degradation of KDM4D, thereby maintaining KDM4D protein levels and H3K9me3 demethylation to regulate proinflammatory cytokine (IL-12, IL-23) expression in dendritic cells. Co-immunoprecipitation, ubiquitination assay, autophagy inhibition/induction experiments, TRIM14-KO and KDM4D-KO dendritic cell studies, mouse autoimmune inflammation model Proceedings of the National Academy of Sciences of the United States of America High 35145029
2021 KDM4D transcriptionally activates SYVN1 expression via H3K9me3 demethylation at the SYVN1 promoter; elevated SYVN1 then mediates ubiquitin-dependent proteasomal degradation of HMGB1, suppressing esophageal squamous cell carcinoma progression. ChIP assay, in vitro ubiquitination assay, shRNA knockdown, xenograft model Frontiers in oncology Medium 34820329
2021 KDM4D regulates MCL-1 expression in AML cells by demethylating H3K9me3 at the MCL-1 promoter region. ChIP assay, shRNA knockdown, cell proliferation and apoptosis assays American journal of translational research Low 34017391
2021 Crystal structures of KDM4D in complex with two inhibitors (OWS and 10r) at 2.0 Å resolution define the active site binding mode and critical pharmacophores, including unique interactions not previously observed. X-ray crystallography Biochemical and biophysical research communications High 33780862
2022 KDM4D (JMJD2D) coactivates SP-1 to promote IFNGR1 expression, which elevates STAT3-IRF1 signaling; JMJD2D also acts as a coactivator of the STAT3-IRF1 axis to enhance PD-L1 transcription in a demethylation activity-dependent manner, promoting colorectal cancer immune escape. Co-immunoprecipitation, ChIP, JMJD2D genetic ablation, tumor infiltrating lymphocyte analysis, xenograft model Oncogene Medium 35027670
2023 SET7/9 methylates KDM4D (JMJD2D) on K427; mutation of K427 reduces prostate cancer cell growth, invasion, and tumor formation and alters transcription of CBLC and PLAGL1, identifying SET7/9 as a writer for KDM4D and K427 methylation as a pro-tumorigenic modification. In vitro methylation assay, site-directed mutagenesis (K427R), cell growth/invasion assays, xenograft model, transcriptomics Frontiers in oncology Medium 38045004
2023 KDM4D (JMJD2D) stabilizes HBx protein by suppressing TRIM14-mediated ubiquitin-proteasome degradation of HBx, and co-occupies HBV cccDNA with HBx as a coactivator to augment HBV cccDNA transcription and replication. Co-immunoprecipitation, ubiquitination assay, ChIP on cccDNA, shRNA knockdown, JMJD2D-KO mouse HBV model JHEP reports : innovation in hepatology Medium 37701334
2023 KDM4D suppresses IAV infection by removing H3K9me3 at the RIG-I promoter and cooperating with NF-κB to enhance RIG-I expression, thus boosting innate antiviral signaling. ChIP assay, shRNA knockdown, KDM4D-KO mouse IAV infection model, Co-immunoprecipitation Biomolecules Medium 42072725
2023 KDM4D interacts with RPS5 and promotes osteo/dentinogenic differentiation of SCAPs; knockdown of KDM4D increases H3K9me2 and H3K9me3 levels at the CNR1 promoter. Co-immunoprecipitation, ChIP, RNA microarray, shRNA knockdown, alizarin red staining, scratch migration assay Oral diseases Low 36579641
2024 KDM4D forms a complex with RPS5 that epigenetically activates CNR1 by demethylating H3K9me2 at its promoter; this enhances mitochondrial membrane potential and energy metabolism to promote osteo/dentinogenic differentiation of DPSCs. Co-immunoprecipitation, ChIP, mitochondrial functional assays (Seahorse, JC-10, TEM), KDM4D/RPS5 overexpression, subcutaneous transplantation in nude mice International endodontic journal Medium 41546606
2024 Under iron-deficient conditions, KDM4D H3K9me3 demethylase activity is reduced, leading to increased H3K9me3 at the PIK3R3 promoter, suppressed PIK3R3 expression, and inhibition of the PI3K-Akt-Foxo1 pathway, thereby blocking quiescent MSC activation. ChIP assay, iron chelation/supplementation, shRNA knockdown, Akt pathway inhibition/rescue, iron-deficient mouse model Cellular and molecular life sciences : CMLS Medium 39158700
2024 X-ray crystallographic mapping of the KDM4D histone-binding pocket with novel tetrazole and pyridine core compounds at high resolution revealed interactions with distal residues in the histone-binding site and a loop movement that blocks accessibility to the histone-binding site upon ligand binding. X-ray crystallography, structure-based drug design European journal of medicinal chemistry High 38981336
2024 KDM4D cooperates with STAT3 to induce IL-17F expression in colonic epithelial cells by being recruited to the IL-17F promoter and demethylating H3K9me3; JMJD2D also promotes STAT3 phosphorylation. Co-immunoprecipitation, ChIP, shRNA knockdown, JMJD2D-KO mouse C. rodentium infection model PLoS pathogens Medium 38905308
2024 Kdm4d mutant male mice are subfertile due to impaired sperm motility; absence of Kdm4d is associated with altered H3K9me3 distribution in round spermatids, indicating Kdm4d-mediated H3K9me3 adjustment is required for generation of motile sperm. Kdm4d knockout mouse generation, sperm motility assay, H3K9me3 immunofluorescence in spermatids, fertilization assays The Journal of reproduction and development Medium 39034148
2023 KDM4D H3K9me2/3 demethylase activity in type I interferon responses: Kdm4d/JMJD2d is associated with enhancer regions genome-wide prior to stimulation and is redistributed to inducible promoters upon activation; depletion attenuates IFN transcriptional response and increases viral susceptibility, while overexpression enhances IFN activation by promoting enhancer RNA transcription and dynamic H3K9me2 demethylation at associated promoters. Knockdown and overexpression in MEFs, epigenomic analyses (ChIP-seq, eRNA assays), viral infection assays Frontiers in immunology Medium 37275914
2025 USP14 deubiquitinase maintains KDM4D protein levels in airway dendritic cells by preventing its ubiquitination-mediated degradation; reduced KDM4D leads to hypermethylation of the Il10 promoter and impaired immune tolerogenic capacity of dendritic cells. ChIP assay, KDM4D-KO DC mouse model, ubiquitination analysis, recombinant USP14 treatment, airway allergy mouse model Cellular immunology Medium 40088847

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D. Biochemical and biophysical research communications 183 17555712
2014 PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair. Proceedings of the National Academy of Sciences of the United States of America 122 24550317
2018 Histone Demethylase JMJD2D Interacts With β-Catenin to Induce Transcription and Activate Colorectal Cancer Cell Proliferation and Tumor Growth in Mice. Gastroenterology 86 30472235
2012 Regulation of tumor suppressor p53 and HCT116 cell physiology by histone demethylase JMJD2D/KDM4D. PloS one 65 22514644
2016 H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication. Nucleic acids research 49 27679476
2018 Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β/VEGFA signalling. Molecular cancer 46 30060750
2015 The emerging role of lysine demethylases in DNA damage response: dissecting the recruitment mode of KDM4D/JMJD2D to DNA damage sites. Cell cycle (Georgetown, Tex.) 44 25714495
2020 Inflammation-induced JMJD2D promotes colitis recovery and colon tumorigenesis by activating Hedgehog signaling. Oncogene 39 32094404
2018 The histone demethylase KDM4D promotes hepatic fibrogenesis by modulating Toll-like receptor 4 signaling pathway. EBioMedicine 36 30527625
2020 Histone demethylase JMJD2D activates HIF1 signaling pathway via multiple mechanisms to promote colorectal cancer glycolysis and progression. Oncogene 35 32989255
2020 Histone demethylase JMJD2D promotes the self-renewal of liver cancer stem-like cells by enhancing EpCAM and Sox9 expression. The Journal of biological chemistry 33 33434575
2014 RNA-dependent chromatin localization of KDM4D lysine demethylase promotes H3K9me3 demethylation. Nucleic acids research 32 25378304
2020 Demethylase-independent function of JMJD2D as a novel antagonist of p53 to promote Liver Cancer initiation and progression. Theranostics 29 32754284
2022 Demethylase JMJD2D induces PD-L1 expression to promote colorectal cancer immune escape by enhancing IFNGR1-STAT3-IRF1 signaling. Oncogene 28 35027670
2022 TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation. Proceedings of the National Academy of Sciences of the United States of America 28 35145029
2020 Histone demethylase KDM4D cooperates with NFIB and MLL1 complex to regulate adipogenic differentiation of C3H10T1/2 mesenchymal stem cells. Scientific reports 20 32080306
2021 Epigenetic Regulator KDM4D Restricts Tumorigenesis via Modulating SYVN1/HMGB1 Ubiquitination Axis in Esophageal Squamous Cell Carcinoma. Frontiers in oncology 19 34820329
2023 Tanshinone I induces ferroptosis in gastric cancer cells via the KDM4D/p53 pathway. Human & experimental toxicology 18 37989263
2020 Histone Lysine Demethylase JMJD2D/KDM4D and Family Members Mediate Effects of Chronic Social Defeat Stress on Mouse Hippocampal Neurogenesis and Mood Disorders. Brain sciences 17 33182385
2016 Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma. Anticancer research 17 27630312
2022 Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers. Cancers 15 35740507
2017 Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3. Bioorganic & medicinal chemistry 15 28434780
2021 Histone demethylase KDM4D inhibition suppresses renal cancer progression and angiogenesis through JAG1 signaling. Cell death discovery 14 34667158
2018 Treatment of donor cells with recombinant KDM4D protein improves preimplantation development of cloned ovine embryos. Cytotechnology 14 29766333
2021 Histone Demethylase KDM4D Could Improve the Developmental Competence of Buffalo (Bubalus Bubalis) Somatic Cell Nuclear Transfer (SCNT) Embryos. Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 13 33478599
2018 KDM4D Predicts Recurrence in Exocrine Pancreatic Cells of Resection Margins from Patients with Pancreatic Adenocarcinoma. Anticancer research 13 29599352
2023 JMJD2D stabilises and cooperates with HBx protein to promote HBV transcription and replication. JHEP reports : innovation in hepatology 12 37701334
2021 Overexpression of KDM4D promotes acute myeloid leukemia cell development by activating MCL-1. American journal of translational research 10 34017391
2023 KDM4D enhances osteo/dentinogenic differentiation and migration of SCAPs via binding to RPS5. Oral diseases 6 36579641
2023 Control of enhancer and promoter activation in the type I interferon response by the histone demethylase Kdm4d/JMJD2d. Frontiers in immunology 5 37275914
2023 Methylation of the epigenetic JMJD2D protein by SET7/9 promotes prostate tumorigenesis. Frontiers in oncology 5 38045004
2022 The TRIM14-USP14-BRCC3 complex epigenetically regulates inflammation through inhibiting OPTN-mediated autophagic degradation of KDM4D. Autophagy 5 35311471
2019 A novel missense mutation within the domain of lysine demethylase 4D (KDM4D) gene is strongly associated with testis morphology traits in pigs. Animal biotechnology 5 30614375
2024 Kdm4d mutant mice show impaired sperm motility and subfertility. The Journal of reproduction and development 4 39034148
2021 Crystal structures of two inhibitors in complex with histone lysine demethylase 4D (KDM4D) provide new insights for rational drug design. Biochemical and biophysical research communications 4 33780862
2024 Histone demethylase JMJD2D protects against enteric bacterial infection via up-regulating colonic IL-17F to induce β-defensin expression. PLoS pathogens 3 38905308
2024 Elevated KDM4D Expression in Pterygium: Impact and Potential Inhibition by Lycium Barbarum Polysaccharide. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 2 38386983
2024 Design, synthesis and biological evaluation of 4,6-diarylquinoxaline-based KDM4D inhibitors. Bioorganic & medicinal chemistry 2 39454559
2023 MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression. Current medical science 2 37828372
2024 Structure-based mapping of the histone-binding pocket of KDM4D using functionalized tetrazole and pyridine core compounds. European journal of medicinal chemistry 1 38981336
2024 Iron-dependent KDM4D activity controls the quiescence-activity balance of MSCs via the PI3K-Akt-Foxo1 pathway. Cellular and molecular life sciences : CMLS 1 39158700
2026 KDM4D-RPS5 Complex Promoted Osteo/Dentinogenic Differentiation of DPSCs via CNR1-Maintained Mitochondrial Functional Homeostasis. International endodontic journal 0 41546606
2026 Kdm4dl is expressed in adult mouse testis and encodes a functional KDM4D-like protein. Biochemical and biophysical research communications 0 42048749
2026 Histone Demethylase JMJD2D Suppresses Influenza A Virus Infection by Promoting RIG-I Expression. Biomolecules 0 42072725
2025 USP14 inhibits sensitization-mediated degradation of KDM4D to epigenetically regulate dendritic cell tolerogenic capacity and mitigates airway allergy. Cellular immunology 0 40088847
2025 Moxibustion regulates KDM4D expression and modulates lipid metabolism to inhibit tumor proliferation in CAC mice. Cancer cell international 0 40325472

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