Affinage

KDM4D

Lysine-specific demethylase 4D · UniProt Q6B0I6

Length
523 aa
Mass
58.6 kDa
Annotated
2026-04-28
44 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM4D (JMJD2D) is a JmjC-domain histone demethylase that removes repressive H3K9me2/me3 marks in an iron- and 2-oxoglutarate-dependent manner, functioning as a transcriptional coactivator for diverse signaling pathways and as a facilitator of DNA damage repair and replication origin licensing. KDM4D is recruited to chromatin through RNA-binding domains and to DNA double-strand break sites via PARP1-dependent ADP-ribosylation and poly(ADP-ribose) binding, where it promotes ATM activation, Rad51 and 53BP1 focus formation, and both homologous recombination and non-homologous end joining (PMID:24550317, PMID:25714495). It physically interacts with and coactivates multiple transcription factors—including AR, β-catenin, Gli2, HIF1α, STAT3, and p53—by demethylating H3K9me3 at their target promoters, while also antagonizing p53 transcriptional activity through a demethylase-independent mechanism that blocks p53 promoter recruitment (PMID:17555712, PMID:30472235, PMID:32094404, PMID:32754284). KDM4D protein stability is regulated by TRIM14-recruited deubiquitinases USP14 and BRCC3, which remove K63-linked ubiquitin chains to prevent OPTN-mediated autophagic degradation, and its activity is further modulated by SET7/9-mediated methylation at K427 (PMID:35145029, PMID:38045004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 High

    Establishing that KDM4D functions as a transcriptional coactivator resolved how this demethylase connects to gene regulation: it physically associates with ligand-bound androgen receptor and stimulates AR-dependent transcription in a catalytic-activity-dependent manner.

    Evidence Co-immunoprecipitation with domain mapping and luciferase reporter assays with catalytic mutants in cell lines

    PMID:17555712

    Open questions at the time
    • Whether coactivation extends to other nuclear receptors beyond AR
    • Genome-wide target identification not performed
    • Structural basis of the AR–KDM4D interaction undefined
  2. 2012 High

    Demonstrating KDM4D interaction with p53 and coactivation of p21 expanded its coactivator repertoire beyond nuclear receptors to tumor suppressors and established dual substrate specificity for H3K9me3/me2 and H1.4K26.

    Evidence In vitro pulldown, co-immunoprecipitation, and luciferase reporter assays with catalytic mutants

    PMID:22514644

    Open questions at the time
    • Whether KDM4D–p53 interaction is activating or inhibitory in vivo remained unresolved until later work
    • H1.4K26 demethylation relevance in endogenous chromatin not tested
  3. 2014 High

    Discovering that KDM4D is rapidly recruited to DNA damage sites via PARP1-mediated ADP-ribosylation and is required for ATM activation, Rad51/53BP1 foci, and both HR and NHEJ revealed a non-transcriptional chromatin-modifying role in the DNA damage response.

    Evidence Live-cell laser microirradiation imaging, co-immunoprecipitation, siRNA knockdown with DR-GFP and EJ5 repair assays

    PMID:24550317

    Open questions at the time
    • Whether demethylase activity is required at damage sites or whether the role is structural
    • Identity of specific H3K9me3-marked loci altered at damage sites unknown
  4. 2014 High

    Identifying two non-canonical RNA-binding domains in KDM4D and showing that N-terminal RNA binding is required for chromatin association established RNA interaction as a prerequisite for KDM4D's epigenetic function.

    Evidence RNA-binding assays, domain-deletion mapping, chromatin fractionation, and H3K9me3 immunofluorescence

    PMID:25378304

    Open questions at the time
    • Identity of specific RNA species that recruit KDM4D to chromatin unknown
    • Whether RNA binding is locus-specific or generic not determined
  5. 2015 Medium

    Showing that KDM4D directly binds poly(ADP-ribose) via its C-terminal region linked the RNA-binding and DNA-damage-recruitment functions, explaining how PARP1 activity recruits KDM4D to break sites.

    Evidence In vitro PAR binding assay and live-cell imaging at laser-induced damage sites with RNA-binding domain mutants

    PMID:25714495

    Open questions at the time
    • Whether PAR binding and RNA binding compete for the same C-terminal surface not resolved
    • In vivo PAR-binding confirmation lacking
  6. 2016 High

    Placing KDM4D at DNA replication origins downstream of ORC/MCM but upstream of Cdc45/PCNA loading revealed a replication-licensing function, demonstrating that H3K9me3 removal is a prerequisite for pre-initiation complex assembly.

    Evidence siRNA knockdown, H3K9M rescue epistasis, co-immunoprecipitation with replication proteins, and ChIP at origins

    PMID:27679476

    Open questions at the time
    • How KDM4D is selectively targeted to active origins versus silent ones
    • Whether this role is cell-cycle-phase restricted
  7. 2018 High

    Multiple studies converged to show KDM4D acts as a coactivator for β-catenin/Wnt and HIF1 pathways by demethylating H3K9me3 at target promoters, establishing it as a broad oncogenic transcriptional coactivator in solid tumors.

    Evidence Co-immunoprecipitation, ChIP, promoter-luciferase assays, Kdm4d KO mouse models (colorectal cancer), and tumor xenografts

    PMID:30060750 PMID:30472235 PMID:32989255

    Open questions at the time
    • Whether KDM4D recruitment to Wnt versus HIF targets involves distinct adaptor proteins
    • Relative contribution of demethylase-dependent versus -independent activities in tumors
  8. 2020 High

    Discovering that KDM4D inhibits p53 recruitment to target promoters independently of its demethylase activity resolved the earlier paradox of KDM4D both coactivating and antagonizing p53, revealing a dual mechanism with opposing transcriptional outcomes.

    Evidence Co-immunoprecipitation, ChIP, EMSA, and Kdm4d KO mouse DEN-induced liver cancer model

    PMID:32754284

    Open questions at the time
    • Structural basis for demethylase-independent p53 sequestration not determined
    • Whether this mechanism operates in non-hepatic tissues
  9. 2020 High

    Identification of KDM4D interactions with Gli2 (Hedgehog) and Notch1-ICD/β-catenin-TCF4 further broadened the signaling pathways coactivated by KDM4D, linking it to intestinal regeneration and cancer stem cell self-renewal.

    Evidence Co-immunoprecipitation, ChIP, Kdm4d KO mouse colitis model, shRNA knockdown with xenograft

    PMID:32094404 PMID:33434575

    Open questions at the time
    • Whether KDM4D binds Gli2 and Notch1-ICD simultaneously or in a mutually exclusive manner
    • No genome-wide binding profile under Hedgehog/Notch stimulation
  10. 2021 High

    Crystal structures of KDM4D with active-site inhibitors at 2.0 Å resolution revealed a ligand-induced loop movement that occludes the histone-binding channel, providing a structural framework for selective inhibitor design.

    Evidence X-ray crystallography at 2.0 Å resolution with two distinct inhibitor scaffolds

    PMID:33780862

    Open questions at the time
    • No co-crystal structure with histone peptide substrate for comparison
    • In vivo efficacy of these inhibitors not reported
  11. 2022 High

    Elucidation of the TRIM14–USP14/BRCC3 deubiquitination axis that prevents K63-linked ubiquitin-mediated autophagic degradation of KDM4D by OPTN revealed how KDM4D protein stability is regulated post-translationally to sustain proinflammatory cytokine production.

    Evidence Co-immunoprecipitation, ubiquitination assays, autophagy flux assays, and dendritic cell-specific KO models

    PMID:35145029

    Open questions at the time
    • Which E3 ligase attaches the K63-linked chains to KDM4D not identified
    • Whether this regulatory axis operates outside dendritic cells
  12. 2023 Medium

    Discovery of SET7/9-mediated methylation of KDM4D at K427 that modulates its oncogenic activity added a non-histone methylation regulatory layer, showing that KDM4D is itself a methylation substrate with functional consequences.

    Evidence In vitro methylation assay, K427R mutagenesis, cell invasion and tumor growth assays, transcriptomics

    PMID:38045004

    Open questions at the time
    • How K427 methylation affects demethylase catalytic activity or protein interactions is mechanistically unclear
    • No structural basis for K427 methylation effect
    • Single lab, not independently confirmed
  13. 2023 Medium

    Showing KDM4D pre-associates with enhancer regions and dynamically redistributes to inducible promoters upon innate immune stimulation to demethylate H3K9me2 and drive enhancer RNA transcription established a role in type I interferon responses.

    Evidence ChIP-seq, RNA-seq, knockdown/overexpression in MEFs, viral susceptibility assay

    PMID:37275914

    Open questions at the time
    • Identity of the signal that triggers KDM4D redistribution from enhancers to promoters
    • Whether this enhancer-priming role extends to other innate immune stimuli beyond IFN
    • Single lab
  14. 2024 Medium

    Demonstrating that Kdm4d KO male mice have impaired sperm motility and altered H3K9me3 distribution in round spermatids established a physiological requirement for KDM4D in male fertility beyond its oncological context.

    Evidence Kdm4d KO mouse, sperm motility assay, H3K9me3 immunofluorescence in spermatids

    PMID:39034148

    Open questions at the time
    • Specific genomic loci where H3K9me3 is aberrantly retained in KO spermatids not mapped
    • Whether the fertility defect is cell-autonomous in germ cells
    • Single lab, not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of RNA species that recruit KDM4D to specific chromatin loci, the E3 ubiquitin ligase responsible for K63-linked ubiquitination of KDM4D, the structural basis for its demethylase-independent p53-antagonist function, and whether its diverse coactivator interactions are competitive or combinatorial at individual promoters.
  • No genome-wide binding analysis under multiple simultaneous signaling inputs
  • Structural basis of KDM4D–transcription factor interfaces unresolved
  • In vivo relevance of H3K79me3 demethylation activity not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 15 GO:0140110 transcription regulator activity 7 GO:0016491 oxidoreductase activity 5 GO:0042393 histone binding 5 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 8 GO:0005694 chromosome 4
Pathway
R-HSA-1643685 Disease 8 R-HSA-4839726 Chromatin organization 8 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 2 R-HSA-1640170 Cell Cycle 1 R-HSA-69306 DNA Replication 1 R-HSA-9612973 Autophagy 1
Partners
ARCTNNB1GLI2HIF1APARP1STAT3TP53TRIM14

Evidence

Reading pass · 29 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, interacting with the AR ligand binding domain, and acts as a coactivator of AR transcriptional activity in a catalytic-activity-dependent manner. Co-immunoprecipitation, domain-mapping pulldown, luciferase reporter assay with catalytic mutants Biochemical and biophysical research communications High 17555712
2012 KDM4D (JMJD2D) demethylates H3K9me3/me2 and H1.4K26 and forms a complex with p53 tumor suppressor (interacting with p53's DNA binding domain), coactivating p53 target gene p21 in a catalytic-activity-dependent manner. In vitro pulldown, co-immunoprecipitation, luciferase reporter with catalytic mutants, cell-based overexpression PloS one High 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 DNA damage, and KDM4D is required for efficient ATM substrate phosphorylation, chromatin association of ATM, Rad51 and p53BP1 foci formation, and both homology-directed repair and NHEJ. Live-cell imaging of laser-induced damage, co-immunoprecipitation, siRNA knockdown with functional DSB repair assays, domain mapping Proceedings of the National Academy of Sciences of the United States of America High 24550317
2014 KDM4D binds RNA via two non-canonical RNA-binding domains (N-terminal aa 115-236 and C-terminal aa 348-523), independent of its demethylase activity; RNA interaction of the N-terminal region is required for KDM4D chromatin association and subsequent H3K9me3 demethylation in cells. RNA-binding assays, domain-deletion mapping, chromatin fractionation, H3K9me3 immunofluorescence in KDM4D mutant-expressing cells Nucleic acids research High 25378304
2015 KDM4D binds poly(ADP-ribose) (PAR) in vitro via its C-terminal region, and this KDM4D-RNA interaction is also required for KDM4D accumulation at DNA breakage sites. In vitro PAR binding assay, live-cell imaging at laser-induced damage sites, RNA interaction domain mutants Cell cycle (Georgetown, Tex.) Medium 25714495
2016 KDM4D demethylates H3K9me3 at DNA replication origins, interacts with replication proteins, and its recruitment depends on pre-replicative complex components ORC and MCM; KDM4D depletion impairs loading of Cdc45, PCNA, and polymerase δ but not ORC/MCM, demonstrating a role in pre-initiative complex formation for DNA replication. siRNA knockdown, H3K9M rescue experiment, co-immunoprecipitation with replication proteins, ChIP at origins, replication assays Nucleic acids research High 27679476
2017 KDM4D was identified as a potential demethylase of H3K79me3 using chemically synthesized trimethylated H3K79 as substrate in an in vitro demethylase assay. Total chemical synthesis of H3K79me3 histone; in vitro demethylase activity assay Bioorganic & medicinal chemistry Medium 28434780
2018 KDM4D (JMJD2D) physically interacts with β-catenin and demethylates H3K9me3 at promoters of β-catenin target genes (MYC, CCND1, MMP2, MMP9) to activate their transcription and promote colorectal cancer cell proliferation. Co-immunoprecipitation, chromatin immunoprecipitation, promoter-luciferase assay, KO mouse models Gastroenterology High 30472235
2018 KDM4D directly interacts with the HIF1β gene promoter and activates HIF1β expression via H3K9me3 and H3K36me3 demethylation, promoting VEGFA-dependent tumor angiogenesis. ChIP assay, luciferase reporter, siRNA knockdown, in vitro and in vivo tumor models Molecular cancer Medium 30060750
2018 KDM4D catalyzes H3K9 di- and tri-demethylation to promote TLR4 expression in hepatic stellate cells, subsequently activating NF-κB signaling and liver fibrogenesis. siRNA knockdown, ChIP, transcriptome analysis, in vivo CCl4 fibrosis model EBioMedicine Medium 30527625
2020 KDM4D (JMJD2D) interacts with Gli2 and reduces H3K9me3 levels at Hedgehog target gene promoters to promote their expression, facilitating colonic regeneration and tumorigenesis. Co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, JMJD2D-KO mouse colitis model Oncogene High 32094404
2020 KDM4D (JMJD2D) activates HIF1 signaling through three mechanisms: (1) cooperating with SOX9 to enhance mTOR expression and HIF1α translation; (2) cooperating with c-Fos to enhance HIF1β transcription; (3) interacting with HIF1α to enhance glycolytic gene expression; all dependent on demethylase activity. siRNA knockdown, rescue overexpression experiments, ChIP, demethylase-defective mutant analysis Oncogene Medium 32989255
2020 KDM4D (JMJD2D) promotes liver cancer stem cell self-renewal by reducing H3K9me3 at the EpCAM promoter via interaction with β-catenin/TCF4, and at the Sox9 promoter via interaction with Notch1 intracellular domain. Co-immunoprecipitation, chromatin immunoprecipitation, shRNA knockdown, rescue experiments, in vivo xenograft The Journal of biological chemistry Medium 33434575
2020 KDM4D (JMJD2D) directly interacts with p53 and inhibits p53 recruitment to the p21 and PUMA promoters in a demethylase-activity-independent manner, acting as a novel p53 antagonist to promote liver cancer. Co-immunoprecipitation, chromatin immunoprecipitation, EMSA, shRNA knockdown, KO mouse DEN-induced liver cancer model Theranostics High 32754284
2020 KDM4D interacts with NFIB and MLL1 complex; KDM4D-mediated demethylation of H3K9me3 at PPARγ and C/EBPα promoters is required for NFIB and MLL1 complex to deposit H3K4me3 and activate adipogenic gene expression, acting upstream of these activators. Co-immunoprecipitation, ChIP, siRNA knockdown, rescue by exogenous expression in C3H10T1/2 cells Scientific reports Medium 32080306
2021 KDM4D transcriptionally activates SYVN1 (an E3 ubiquitin ligase) via H3K9me3 demethylation at its promoter, which then triggers ubiquitin-dependent degradation of HMGB1, suppressing esophageal squamous cell carcinoma progression. ChIP, in vitro ubiquitination assay, shRNA knockdown, in vivo xenograft Frontiers in oncology Medium 34820329
2021 KDM4D demethylates H3K9me3 at the MCL-1 promoter to promote MCL-1 expression in acute myeloid leukemia cells. ChIP, siRNA knockdown, cell proliferation and apoptosis assays American journal of translational research Medium 34017391
2021 KDM4D directly interacts with the JAG1 promoter and upregulates VEGFR-3 expression to promote tumor angiogenesis in clear cell renal cell carcinoma. ChIP, siRNA knockdown, in vitro angiogenesis assay, in vivo xenograft Cell death discovery Low 34667158
2021 Crystal structures of KDM4D in complex with two inhibitors (OWS and 10r) at 2.0 Å resolution revealed inhibitor binding modes within the active site and a loop movement that blocks the histone-binding site upon ligand binding. X-ray crystallography at 2.0 Å Biochemical and biophysical research communications High 33780862
2022 TRIM14 recruits deubiquitinases USP14 and BRCC3 to cleave K63-linked ubiquitin chains on KDM4D, preventing KDM4D from undergoing OPTN-mediated selective autophagy, thereby stabilizing KDM4D and sustaining H3K9me3 demethylation and proinflammatory cytokine (IL-12, IL-23) expression. Co-immunoprecipitation, ubiquitination assay, autophagy flux assay, dendritic cell KO models Proceedings of the National Academy of Sciences of the United States of America High 35145029
2022 KDM4D (JMJD2D) coactivates SP-1 to promote IFNGR1 expression, which elevates STAT3-IRF1 signaling; JMJD2D also acts as a coactivator for the STAT3-IRF1 axis to enhance PD-L1 transcription in a demethylation-activity-dependent manner. Co-immunoprecipitation, ChIP, siRNA knockdown, demethylase-mutant rescue, in vivo tumor models with CD8+ T cell infiltration analysis 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 downstream targets including CBLC and PLAGL1. In vitro methylation assay, site-directed mutagenesis (K427R), cell invasion and tumor growth assays, transcriptomic analysis Frontiers in oncology Medium 38045004
2023 KDM4D (JMJD2D) stabilizes HBx protein by suppressing TRIM14-mediated ubiquitin-proteasome degradation, and acts as a co-activator of HBx on cccDNA to augment HBV transcription and replication. Co-immunoprecipitation, ubiquitylation assay, ChIP on cccDNA, siRNA knockdown in HBV-infected cells, KO mouse HBV model JHEP reports High 37701334
2023 KDM4D cooperates with STAT3 and is recruited to the IL-17F promoter to demethylate H3K9me3, inducing IL-17F expression and subsequently β-defensin expression for host defense against enteric bacterial infection. Co-immunoprecipitation, ChIP, shRNA knockdown, JMJD2D-KO mouse Citrobacter rodentium infection model PLoS pathogens Medium 38905308
2023 KDM4D is a positive regulator of type I interferon responses; it is pre-associated with enhancer regions and redistributes to inducible promoters upon stimulation, promoting enhancer RNA transcription and dynamic H3K9me2 demethylation at associated promoters. Knockdown and overexpression in MEFs, epigenomic analyses (ChIP-seq, RNA-seq), viral susceptibility assay Frontiers in immunology Medium 37275914
2024 X-ray crystal structures of KDM4D bound to novel inhibitors (tetrazole and pyridine core compounds) revealed that flexible tails probe distal residues in the histone-binding site and a prominent loop movement blocks histone-binding site accessibility upon ligand binding. X-ray crystallography European journal of medicinal chemistry High 38981336
2024 KDM4D is required for male fertility; Kdm4d mutant male mice show impaired sperm motility and subfertility, associated with altered H3K9me3 distribution in round spermatids, demonstrating KDM4D-mediated H3K9me3 adjustment is needed for motile sperm generation. Kdm4d KO mouse generation, sperm motility assay, H3K9me3 immunofluorescence in spermatids The Journal of reproduction and development Medium 39034148
2024 KDM4D's H3K9me3 demethylase activity is iron-dependent; under iron deficiency, KDM4D activity decreases, increasing H3K9me3 at the PIK3R3 promoter, suppressing PIK3R3 expression and inhibiting quiescent MSC activation via the PI3K-Akt-Foxo1 pathway. Iron chelation experiments, ChIP at PIK3R3 promoter, PI3K-Akt-Foxo1 pathway rescue, iron-deficient mouse model with bone mass measurement Cellular and molecular life sciences Medium 39158700
2023 KDM4D binds RPS5 physically via a specific structural domain and the KDM4D-RPS5 complex promotes osteo/dentinogenic differentiation of stem cells of the apical papilla; ChIP showed KDM4D demethylates H3K9me2/me3 at the CNR1 promoter, and disruption of the KDM4D-RPS5 binding abolishes differentiation. Co-immunoprecipitation, ChIP, shRNA knockdown, overexpression, alizarin red staining Oral diseases Medium 36579641

Source papers

Stage 0 corpus · 44 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 182 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 121 24550317
2018 Histone Demethylase JMJD2D Interacts With β-Catenin to Induce Transcription and Activate Colorectal Cancer Cell Proliferation and Tumor Growth in Mice. Gastroenterology 85 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 45 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.) 43 25714495
2020 Inflammation-induced JMJD2D promotes colitis recovery and colon tumorigenesis by activating Hedgehog signaling. Oncogene 38 32094404
2018 The histone demethylase KDM4D promotes hepatic fibrogenesis by modulating Toll-like receptor 4 signaling pathway. EBioMedicine 35 30527625
2020 Histone demethylase JMJD2D activates HIF1 signaling pathway via multiple mechanisms to promote colorectal cancer glycolysis and progression. Oncogene 33 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 32 33434575
2014 RNA-dependent chromatin localization of KDM4D lysine demethylase promotes H3K9me3 demethylation. Nucleic acids research 31 25378304
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 Demethylase-independent function of JMJD2D as a novel antagonist of p53 to promote Liver Cancer initiation and progression. Theranostics 28 32754284
2022 Demethylase JMJD2D induces PD-L1 expression to promote colorectal cancer immune escape by enhancing IFNGR1-STAT3-IRF1 signaling. Oncogene 27 35027670
2020 Histone demethylase KDM4D cooperates with NFIB and MLL1 complex to regulate adipogenic differentiation of C3H10T1/2 mesenchymal stem cells. Scientific reports 20 32080306
2023 Tanshinone I induces ferroptosis in gastric cancer cells via the KDM4D/p53 pathway. Human & experimental toxicology 17 37989263
2021 Epigenetic Regulator KDM4D Restricts Tumorigenesis via Modulating SYVN1/HMGB1 Ubiquitination Axis in Esophageal Squamous Cell Carcinoma. Frontiers in oncology 17 34820329
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
2017 Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3. Bioorganic & medicinal chemistry 15 28434780
2022 Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers. Cancers 14 35740507
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 11 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 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
2023 Control of enhancer and promoter activation in the type I interferon response by the histone demethylase Kdm4d/JMJD2d. Frontiers in immunology 4 37275914
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 Kdm4d mutant mice show impaired sperm motility and subfertility. The Journal of reproduction and development 3 39034148
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 Histone demethylase JMJD2D protects against enteric bacterial infection via up-regulating colonic IL-17F to induce β-defensin expression. PLoS pathogens 2 38905308
2024 Design, synthesis and biological evaluation of 4,6-diarylquinoxaline-based KDM4D inhibitors. Bioorganic & medicinal chemistry 2 39454559
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
2023 MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression. Current medical science 1 37828372
2026 KDM4D-RPS5 Complex Promoted Osteo/Dentinogenic Differentiation of DPSCs via CNR1-Maintained Mitochondrial Functional Homeostasis. International endodontic journal 0 41546606
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