Affinage

ZMYND8

MYND-type zinc finger-containing chromatin reader ZMYND8 · UniProt Q9ULU4

Length
1186 aa
Mass
131.7 kDa
Annotated
2026-04-28
51 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZMYND8 is a multivalent chromatin reader and transcriptional regulator that integrates histone mark recognition with recruitment of chromatin-modifying complexes to control enhancer activity, DNA damage repair, and gene expression programs across diverse cell types. Its PHD-BRD-PWWP supramodule forms a rigid structural unit that simultaneously engages combinatorial histone modifications (H3K4me1-H3K14ac, H3K36me2, H4K16ac) and DNA, while its MYND domain directly binds PPPLΦ motifs in the NuRD subunit GATAD2A; homodimerization via the coiled-coil domain switches ZMYND8 between an activating P-TEFb-associated state and a repressive NuRD/CHD4-associated state (PMID:27926874, PMID:27732854, PMID:30134174, PMID:41999894). At DNA double-strand breaks, KDM5A-mediated H3K4me3 demethylation and poly(ADP-ribose) signaling recruit ZMYND8-NuRD to silence transcription at damaged active chromatin and promote homologous recombination, while at enhancers ZMYND8 cooperates with KDM5C, BRD4, PRC2, and Mediator to modulate super-enhancer output, cholesterol biosynthesis, and immune gene regulation (PMID:25593309, PMID:28572115, PMID:27058665, PMID:34358447, PMID:33932349, PMID:40125808). ZMYND8 protein stability is controlled by FBXW7-mediated polyubiquitination counteracted by USP7- and OTUD4-dependent deubiquitination, and its chromatin engagement is regulated by p300-mediated acetylation at K1007/K1034 and cytoplasmic sequestration by Drebrin (PMID:34487730, PMID:39128723, PMID:29629903, PMID:28966017).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2010 Medium

    Establishing ZMYND8 as a transcriptional repressor with neuronal relevance: before this, ZMYND8 lacked functional characterization beyond PKCβI binding; interaction with RCOR2 and neural differentiation inhibition upon overexpression placed it in a repressive transcriptional context.

    Evidence Yeast two-hybrid and Co-IP in Xenopus, embryo overexpression with neural differentiation readout

    PMID:20331974

    Open questions at the time
    • Not replicated independently
    • Mammalian relevance of RCOR2 interaction not confirmed
    • Mechanism of repression undefined
  2. 2015 High

    Defining ZMYND8 as a DNA damage-responsive factor that recruits NuRD to silence transcription at breaks and promote HR resolved a key question about how transcriptionally active chromatin is silenced during repair.

    Evidence Fluorescence microscopy localization screen, Co-IP with NuRD, ChIP, HR repair assays in human cells

    PMID:25593309

    Open questions at the time
    • Upstream signal triggering ZMYND8 recruitment not yet defined
    • Histone mark specificity at damage sites unclear
  3. 2016 High

    Structural and biochemical dissection of the PHD-BRD-PWWP supramodule as a rigid multivalent reader that simultaneously engages histone PTMs and DNA explained how ZMYND8 achieves chromatin targeting specificity; parallel work defined H3K4me1-H3K14ac as a preferred dual mark and mapped the MYND-GATAD2A interface.

    Evidence X-ray crystallography of the triple reader cassette, histone peptide pulldowns and mutagenesis, mass spectrometry interactome with GATAD2A domain mapping, live-cell DNA damage recruitment

    PMID:27477906 PMID:27732854 PMID:27926874

    Open questions at the time
    • Full-length ZMYND8 structure unresolved
    • Contribution of DNA binding versus histone binding in vivo not quantitated
  4. 2016 High

    Discovering that ZMYND8 partners with KDM5C at active enhancers and super-enhancers, where their loss causes H3K4me3 gain and enhancer overactivation, established ZMYND8 as a guardian of enhancer homeostasis beyond DNA damage.

    Evidence Co-purification, ChIP-seq, RNA-seq with KO/KD in breast cancer cells

    PMID:27058665

    Open questions at the time
    • Whether KDM5C and KDM5A act redundantly at enhancers unknown
    • Mechanism of ZMYND8-KDM5C cooperation not structurally resolved
  5. 2017 High

    KDM5A-mediated H3K4me3 demethylation was shown to be prerequisite for ZMYND8-NuRD binding at DSBs, placing ZMYND8 downstream of a histone demethylation step and explaining mark-dependent recruitment; the Drebrin crystal structure revealed a cytoplasmic sequestration mechanism that competes with chromatin binding.

    Evidence KDM5A KD with epistasis to ZMYND8/HR, ChIP; X-ray crystallography of Drebrin ADF-H–ZMYND8 complex with competitive binding and localization assays

    PMID:28572115 PMID:28966017

    Open questions at the time
    • Physiological conditions triggering Drebrin-mediated sequestration unknown
    • Whether KDM5A acts catalytically or as a scaffold not fully distinguished
  6. 2018 High

    A dimerization-dependent functional switch was uncovered: homodimeric ZMYND8 associates with P-TEFb via CyclinT1 to activate transcription, while monomeric ZMYND8 binds CHD4/NuRD to repress, resolving the paradox of ZMYND8 acting as both activator and repressor.

    Evidence Biochemical reconstitution of ZMYND8-P-TEFb, coiled-coil domain mutagenesis, reporter assays, ATRA differentiation

    PMID:30134174

    Open questions at the time
    • What controls the dimer–monomer equilibrium in vivo is unknown
    • Structural basis of CyclinT1 interaction not determined
  7. 2018 High

    p300-mediated acetylation of ZMYND8 at K1007/K1034 was shown to be required for HIF transcriptional activation and BRD4 recruitment, establishing post-translational regulation of ZMYND8 coactivator function and linking it to hypoxic oncogenesis; separately, ZMYND8 was found to regulate Igh super-enhancer activity controlling class switch recombination and somatic hypermutation in B cells.

    Evidence K-to-R site mutagenesis with in vitro acetylation, ChIP, Pol II pausing analysis, mouse metastasis model; B cell-specific KO with CSR/SHM assays

    PMID:29629903 PMID:30293785

    Open questions at the time
    • Whether acetylation-dependent and dimerization-dependent activation are the same pathway is unclear
    • Acetylation dynamics and opposing deacetylase not identified
  8. 2020 High

    ZMYND8 was found to recognize the oncohistone H3.3G34R mutation, suppressing CIITA and MHC-II expression; loss of ZMYND8 triggered cGAS-STING innate immune signaling via micronucleus formation, revealing ZMYND8 as a genome stability factor with immune-evasion consequences.

    Evidence In vitro binding and ChIP-seq for H3.3G34R recognition, CRISPR knock-in correction; ZMYND8 KO with micronucleus assay and cGAS-STING pathway analysis in syngeneic tumor models

    PMID:32832624 PMID:33148660

    Open questions at the time
    • Structural basis of H3.3G34R recognition not resolved
    • Whether genome instability is direct or via transcriptional deregulation unknown
  9. 2021 High

    ZMYND8 was shown to directly interact with BRD4's ET domain in AML and to cooperate with SREBP2 and Mediator at enhancer-promoter loops for cholesterol biosynthesis, broadening its role to lineage-specific transcriptional activation and metabolic gene regulation.

    Evidence Reciprocal Co-IP with BRD4 domain mapping, ChIP-seq in AML patient samples, in vivo AML model; HiChIP, Mediator Co-IP, ZMYND8 KO with metabolic and tumorigenesis readout

    PMID:33932349 PMID:34358447

    Open questions at the time
    • Whether BRD4-ET and P-TEFb interactions are concurrent or mutually exclusive unknown
    • Mediator subunit specificity not defined
  10. 2022 Medium

    FBXW7 was identified as the E3 ligase that polyubiquitinates and degrades ZMYND8, and clinically observed ZMYND8 missense variants were shown to disrupt specific domain interactions (PWWP–Drebrin, MYND–GATAD2A), with a Drosophila ortholog knockdown linking ZMYND8 to habituation learning.

    Evidence Co-IP and ubiquitination assays for FBXW7; yeast two-hybrid with patient variants and Drosophila neuronal KD with behavioral phenotype

    PMID:34487730 PMID:35916866

    Open questions at the time
    • FBXW7 degron motif on ZMYND8 not mapped
    • Mammalian neurological phenotype of ZMYND8 loss not established
    • ZMYND8 variant pathogenicity not confirmed in mammalian neurons
  11. 2024 High

    USP7 was identified as the deubiquitinase that directly reverses FBXW7-catalyzed polyubiquitination at K1034, stabilizing ZMYND8; a ZMYND8-NRF2 positive feedback loop was shown to suppress ferroptosis in breast cancer stem cells, connecting ZMYND8 to redox homeostasis.

    Evidence In vitro deubiquitination assay with domain mapping and K1034 mutagenesis; reciprocal Co-IP of ZMYND8-NRF2, ChIP, ROS and ferroptosis assays

    PMID:38488001 PMID:39128723

    Open questions at the time
    • Whether USP7-ZMYND8 interaction is regulated by signaling is unknown
    • Structural basis of K1034 ubiquitination/deubiquitination not resolved
  12. 2025 High

    ZMYND8 was shown to interact with PRC2 to establish H3K27me3 domains in astrocytes, to dynamically redistribute to activated enhancers upon stimulation, and to cooperate with FOXM1 and SWI/SNF in driving neuroendocrine prostate cancer transdifferentiation, revealing context-dependent partnerships with multiple chromatin-modifying complexes.

    Evidence Conditional KO with ChIP-seq for PRC2/H3K27me3 in astrocytes; acute stimulation ChIP-seq; CRISPR screen with scRNA-seq and small molecule ZMYND8 inhibitor in NEPC models

    PMID:40102673 PMID:40125808 PMID:40734674

    Open questions at the time
    • How ZMYND8 selects between NuRD, PRC2, P-TEFb, BRD4, and SWI/SNF at individual loci is unclear
    • Therapeutic window and selectivity of iZMYND8-34 not established
  13. 2025 High

    The coiled-coil MYND domain crystal structure confirmed homodimeric architecture and provided quantitative binding parameters for GATAD2A recognition; parallel studies extended ZMYND8 transcriptional programs to WNT/β-catenin signaling, phospholipid metabolism, and unfolded protein response suppression.

    Evidence X-ray crystallography of CC-MYND with quantitative binding; Co-IP with DDX3X-CK1ε for WNT; ChIP and metabolomics for cPLA2α/IL-27 axis; PWWP mutagenesis linking H3K36me2 to CEBPE and UPR

    PMID:40281007 PMID:40347515 PMID:41297414 PMID:41999894

    Open questions at the time
    • Full-length ZMYND8 structure including disordered regions remains undetermined
    • Relative contribution of each target gene program to overall ZMYND8 biology in normal physiology unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Unresolved: how ZMYND8 selects among its many chromatin-remodeling partners (NuRD, PRC2, SWI/SNF, P-TEFb, BRD4, Mediator) at individual genomic loci, and whether the dimer–monomer switch fully explains this selectivity, remain central open questions.
  • Full-length structural model needed to understand allosteric regulation across domains
  • In vivo stoichiometry and dynamics of partner switching uncharacterized
  • Normal physiological role of ZMYND8 in non-cancer tissues (brain, immune, cardiac) remains poorly defined genetically in mammals

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0042393 histone binding 5 GO:0060090 molecular adaptor activity 5
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 4 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-4839726 Chromatin organization 5 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 1
Partners
BRD4CHD4DBN1FBXW7GATAD2AKDM5AKDM5CUSP7
Complex memberships
NuRD complex (via GATAD2A/CHD4)P-TEFb complex (via CyclinT1)PRC2 complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 ZMYND8 bromodomain changes localization in response to DNA damage and recruits the NuRD (nucleosome remodeling and histone deacetylation) complex to damaged chromatin to repress transcription and promote repair by homologous recombination at transcriptionally active regions. Fluorescence microscopy (localization screen), Co-IP, ChIP, HR repair assays, knockdown with defined phenotypic readout Genes & development High 25593309
2016 ZMYND8 (RACK7) forms a biochemical complex with the histone H3K4me3-specific demethylase KDM5C and occupies active enhancers including super-enhancers; loss of RACK7 or KDM5C causes enhancer overactivation characterized by H3K4me3 and H3K27Ac deposition and increased eRNA transcription. Biochemical co-purification, ChIP-seq, RNA-seq, KO/KD with defined chromatin and transcriptional phenotype Cell High 27058665
2016 ZMYND8 PHD-Bromodomain cassette recognizes the dual histone mark H3K4me1-H3K14ac (and H3K4me0-H3K14ac) and acts as a transcriptional co-repressor by recruiting histone demethylase JARID1D, antagonizing expression of metastasis-linked genes. Histone peptide pulldown, Co-IP, domain mutagenesis, ChIP-seq, invasion assays in vitro and in vivo Molecular cell High 27477906
2017 Histone demethylase KDM5A demethylates H3K4me3 near DNA double-strand breaks, and this demethylation is required for ZMYND8-NuRD binding to chromatin and recruitment to damage sites; KDM5A deficiency impairs ZMYND8-NuRD-dependent transcriptional silencing and HR repair. ChIP, Co-IP, KDM5A KD with HR repair assay, epistasis between KDM5A and ZMYND8-NuRD The Journal of cell biology High 28572115
2016 The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A, bridging ZMYND8 to specific NuRD subcomplexes; GATAD2A and GATAD2B form mutually exclusive NuRD subcomplexes, and the MYND domain facilitates poly(ADP-ribose)-dependent rapid recruitment of GATAD2A/NuRD to DNA damage sites to promote HR. Mass spectrometry interactome, Co-IP, domain mutagenesis, live-cell imaging at laser-induced DSBs, PARP inhibition Cell reports High 27732854
2016 Crystal structure of the ZMYND8 PHD-BRD-PWWP triple reader cassette reveals a rigid structural supramodule that simultaneously engages multiple histone PTMs and DNA; disruption of any single domain impairs multivalent chromatin engagement and recruitment to DNA damage sites. X-ray crystallography, histone peptide binding assays, domain mutagenesis, live-cell DNA damage recruitment assay Cell reports High 27926874
2015 ZMYND8 selectively reads H3.1K36me2/H4K16ac marks through its conserved chromatin-binding modules and is recruited to ATRA-responsive developmental gene promoters; ZMYND8 interacts with Ser5-phosphorylated (initiation-competent) RNA Pol II in a DNA template-dependent manner to modulate transcription. Histone peptide pulldown, Co-IP with RNA Pol II CTD, ChIP, ATRA treatment, domain mutagenesis The Journal of biological chemistry Medium 26655721
2018 ZMYND8 interacts with HIF-1α and HIF-2α and promotes elongation of HIF-induced oncogenic genes by increasing BRD4 recruitment and release of paused RNA Pol II; ZMYND8 acetylation at K1007 and K1034 by p300 is required for HIF activation and breast cancer progression. Co-IP, ChIP, RNA Pol II pausing analysis, acetylation site mutagenesis (K→R), in vitro acetylation assay, mouse metastasis model The Journal of clinical investigation High 29629903
2018 ZMYND8, through direct association with CyclinT1, forms a ZMYND8-P-TEFb complex that activates transcription; ZMYND8 homodimerizes via its coiled-coil domain to preferentially associate with P-TEFb (activator), while the monomer associates with CHD4/NuRD (repressor), providing a dual activator/repressor switch. Biochemical reconstitution, Co-IP, reporter gene assay, domain mutagenesis (coiled-coil), ATRA-induced differentiation assay Cell reports High 30134174
2017 Crystal structure of Drebrin ADF-H domain in complex with ZMYND8 PHD-BRD-PWWP supramodule shows that Drebrin ADF-H competes with modified histones for ZMYND8 binding and can shuttle ZMYND8 from nucleus to cytoplasm, suggesting cytoplasmic sequestration as a regulatory mechanism. X-ray crystallography, competitive binding assay, live-cell fluorescence imaging (nuclear-cytoplasmic fractionation) Structure High 28966017
2010 In Xenopus, ZMYND8 was identified as a binding partner of RCOR2 via yeast two-hybrid and confirmed by Co-IP; both proteins function as transcriptional repressors and co-localize in the nervous system; overexpression of XZMYND8 inhibits neural differentiation in Xenopus embryos. Yeast two-hybrid screen, Co-IP, overexpression in Xenopus embryos with neural differentiation readout Biochemical and biophysical research communications Medium 20331974
2000 PRKCBP1 (ZMYND8) was identified as a RACK family protein whose carboxy terminus interacts specifically with PKCβI by GST pulldown/immunoprecipitation assay. GST pulldown, immunoprecipitation with GST-fused PRKCBP1 Mammalian genome Low 11003709
2018 ZMYND8 binds to and regulates the 3' Igh super-enhancer (3'RR) in B cells, controlling its transcriptional status; ZMYND8 deficiency increases polymerase loading at the 3'RR but decreases acceptor region transcription, impairing both class switch recombination and somatic hypermutation. ChIP-seq, B cell-specific KO mice, CSR and SHM assays, RNA Pol II ChIP Molecular cell High 30293785
2019 The lncRNA TROJAN binds to ZMYND8 and increases its degradation through the ubiquitin-proteasome pathway by repelling the stabilizing factor ZNF592, thereby upregulating ZMYND8 target metastasis-related genes in TNBC. RNA pulldown, Co-IP, ubiquitination assay, ZNF592 interaction studies, gene expression analysis Science advances Medium 30854423
2020 RACK7 (ZMYND8) recognizes histone H3.3G34R patient mutation in vitro and in vivo, and binding of RACK7 to H3.3G34R suppresses transcription of CIITA and downstream MHC class II genes; CRISPR knock-in correction of H3.3G34R reduces RACK7 chromatin binding and derepresses these genes. In vitro binding assay, ChIP-seq, CRISPR knock-in correction, RACK7 KO in patient-derived cells Science advances High 32832624
2021 ZMYND8 binds to EZH2, and this interaction is enhanced by CDK1-mediated phosphorylation of EZH2 at T487; ZMYND8 is required for EZH2-FOXM1 interaction and FOXM1-dependent MMP gene expression and cancer cell migration, constituting a polycomb-independent oncogenic switch. Co-IP, CDK1 phosphorylation assay, ZMYND8 KD with FOXM1/MMP expression and migration readout, domain mapping PNAS Medium 33593912
2021 ZMYND8 directly activates IRF8 and MYC through their lineage-specific enhancers in AML; ZMYND8 binds the ET domain of BRD4 via its chromatin reader cassette, and this interaction is required for proper chromatin occupancy and maintenance of AML proliferation. ChIP-seq in cell lines and patient samples, BRD4 Co-IP/domain mapping, ZMYND8 KO with in vitro and in vivo AML proliferation assay Molecular cell High 34358447
2021 ZMYND8 and SREBP2 drive enhancer-promoter interaction to recruit the Mediator complex and upregulate mevalonate pathway genes; loss of ZMYND8 restricts cholesterol biosynthesis and intestinal tumorigenesis in a YAP-dependent context. ChIP-seq, HiChIP (enhancer-promoter interaction), Co-IP with Mediator, ZMYND8 KO with metabolic and tumorigenesis readout Molecular cell High 33932349
2021 E3 ubiquitin ligase FBXW7 directly interacts with ZMYND8 and degrades it via polyubiquitination, controlling ZMYND8 protein stability; low FBXW7 leads to ZMYND8 accumulation promoting bladder cancer progression. Co-IP, ubiquitination assay, FBXW7/ZMYND8 interaction mapping, KD/KO with tumor growth readout Experimental cell research Medium 34487730
2020 ZMYND8 maintains genome stability in breast cancer cells; ZMYND8 loss triggers micronucleus formation, activation of cGAS in micronuclei, and downstream STING/NF-κB signaling (but not TBK1/IRF3), inducing IFNβ and ISG expression and promoting CD4+/CD8+ T cell infiltration and tumor inhibition. ZMYND8 KO with micronucleus assay, cGAS/STING pathway analysis, in vivo syngeneic tumor model with T cell depletion Cancer research Medium 33148660
2022 ZMYND8 is a master transcriptional regulator of 27-hydroxycholesterol metabolism, increasing cholesterol biosynthesis/oxidation and blocking efflux/catabolism; 27-HC accumulation activates liver X receptor to promote EMT and tumor initiation. ZMYND8 KO in mouse mammary tumor models, metabolomics, ChIP, gene expression with LXR pathway assays Science advances Medium 35857506
2024 ZMYND8 increases NRF2 protein stability by silencing KEAP1 (indirect), and also directly interacts with NRF2 and recruits it to promoters of antioxidant genes; NRF2 in turn directly controls ZMYND8 expression, forming a positive feedback loop that sustains BCSC survival by inhibiting ROS and ferroptosis. Co-IP (ZMYND8-NRF2), ChIP, ZMYND8/NRF2 KO/KD with ROS and ferroptosis assays, mammosphere formation The Journal of clinical investigation High 38488001
2024 USP7 directly binds the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF and UBL domains and removes FBXW7-catalyzed poly-ubiquitin chains at K1034 of ZMYND8, stabilizing ZMYND8 and stimulating transcription of target genes ZEB1 and VEGFA to enhance breast cancer migration and invasion. Co-IP with domain mapping, in vitro deubiquitination assay, site-specific mutagenesis (K1034), target gene expression and migration assays The Journal of biological chemistry High 39128723
2022 ARID1A-containing BAF complexes maintain histone H3.3 at super-enhancers; ARID1A is required for CHD4 (NuRD) recruitment to H3.3-marked regions; ZMYND8 interacts with CHD4 to suppress a subset of H3.3+/H4K16ac+ super-enhancers regulating EMT-related genes. ChIP-seq, ATAC-seq, H3.3 native ChIP, ARID1A KD epistasis with CHD4 and ZMYND8 Co-IP BMC biology Medium 36153585
2022 Missense variants in the PWWP domain of ZMYND8 abolish its interaction with Drebrin, and missense variants in the MYND domain disrupt the interaction with GATAD2A; neuronal knockdown of the Drosophila ZMYND8 ortholog causes decreased habituation learning. Yeast two-hybrid assay, molecular modeling, Drosophila neuronal knockdown with behavioral phenotype Genetics in medicine Medium 35916866
2025 FOXM1 stabilizes ZMYND8 binding to H3K4me1-H3K14ac-marked chromatin; antiandrogen therapy releases SWI/SNF from the androgen receptor, enabling SWI/SNF interaction with ZMYND8-FOXM1 to upregulate neuroendocrine lineage regulators, driving NEPC transdifferentiation. CRISPR-Cas9 screen combined with scRNA-seq, ChIP-seq, Co-IP (ZMYND8-FOXM1-SWI/SNF), small molecule inhibitor iZMYND8-34 in NEPC models Nature cancer High 40102673
2025 ZMYND8 enhances cPLA2α expression through c-Myc induction; cPLA2α inactivates phosphatidylcholine-specific phospholipase C, reducing phosphatidylcholine breakdown to diacylglycerol, which diminishes PKC activity and leads to IL-27 secretion conferring trastuzumab/pertuzumab resistance. ChIP, Co-IP, cPLA2α KD/KO with phospholipid metabolite measurements, IL-27 rescue experiments, patient-derived organoids, PDX models Nature communications High 40281007
2025 RACK7 (ZMYND8) interacts with PRC2 complex and establishes genomic localization of SUZ12 and H3K27 methylation in astrocytes; Rack7 deletion in astrocytes causes genome-wide decrease in H3K27me3 and derepression of Wnt signaling pathway genes, impairing astrocyte development. Conditional KO mouse model, Co-IP (RACK7-PRC2), ChIP-seq (H3K27me3, SUZ12), RNA-seq Advanced science High 40125808
2025 ZMYND8 interacts with c-Myc directly and activates c-Myc transcriptional activity to promote the Warburg effect in pancreatic cancer; ZMYND8 physically associates with c-Myc as shown by Co-IP and proteomic profiling. Co-IP, proteomics, CUT&Tag, RNA-seq, in vivo xenograft with c-Myc KD rescue Oncogene Medium 40579459
2025 ZMYND8's PWWP domain reads H3K36me2 and activates CEBPE transcription in an H3K36me2-dependent manner; ZMYND8-driven CEBPE expression suppresses adaptive UPR pathways (ERN1, XBP1, ATF6) to inhibit multiple myeloma cell survival. Co-IP, ChIP, domain mutagenesis (PWWP), CUT&RUN, RNA-seq, KD/KO with UPR and proliferation assays Advanced science Medium 40347515
2025 ZMYND8 mediates ubiquitination and proteasomal degradation of HMGB1 in cardiomyocytes; trametinib (MEK inhibitor) inhibits ZMYND8-mediated ubiquitination of HMGB1, causing its accumulation and cardiomyocyte death. Co-IP, ubiquitination assay, ZMYND8 KD/KO in cardiomyocytes, HMGB1 stability assay, cardiac function readout in mice Biochemical pharmacology Medium 41423035
2026 Crystal structure of the ZMYND8 coiled-coil MYND domain reveals a homodimeric architecture; the MYND domain recognizes proline-rich motifs in GATAD2A's central region with moderate affinity enhanced by multivalency; ZMYND8 recruits GATAD2A specifically to the MAPT213 internal regulatory region to suppress MAPT213 lncRNA transcription while promoting MAPT protein-coding transcript expression. X-ray crystallography, ChIP, Co-IP, domain mutagenesis, quantitative binding measurements The Journal of biological chemistry High 41999894
2025 RACK7 rapidly redistributes from repressed to activated enhancers in response to acute stimulations in a transcription-dependent manner and positively regulates enhancer activation by promoting RNA Pol II recruitment. ChIP-seq under acute stimulation conditions, RNA Pol II ChIP, transcription inhibitor experiments iScience Medium 40734674
2025 OTUD4 deubiquitinase directly interacts with and stabilizes ZMYND8; ZMYND8 acts as a scaffold promoting DDX3X-CK1ε complex assembly and WNT/β-catenin activation, which upregulates CSF1 to promote M2 macrophage polarization and immunosuppressive niche formation in TNBC spinal metastasis. Co-IP, deubiquitination assay, ZMYND8 KD with WNT signaling and macrophage polarization readout, in vivo spinal metastasis model Neoplasia Medium 41297414

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination. Genes & development 203 25593309
2016 Suppression of Enhancer Overactivation by a RACK7-Histone Demethylase Complex. Cell 155 27058665
2018 ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis. The Journal of clinical investigation 141 29629903
2017 Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair. The Journal of cell biology 137 28572115
2016 ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes. Molecular cell 122 27477906
2019 The endogenous retrovirus-derived long noncoding RNA TROJAN promotes triple-negative breast cancer progression via ZMYND8 degradation. Science advances 99 30854423
2016 ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage. Cell reports 96 27732854
2016 Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin. Cell reports 77 27926874
2015 Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8. The Journal of biological chemistry 62 26655721
2021 ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency. Molecular cell 52 34358447
2021 The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability. Molecular cell 48 33932349
2024 ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2. The Journal of clinical investigation 47 38488001
2000 Identification and characterization of PRKCBP1, a candidate RACK-like protein. Mammalian genome : official journal of the International Mammalian Genome Society 42 11003709
2018 Positive Regulation of Transcription by Human ZMYND8 through Its Association with P-TEFb Complex. Cell reports 38 30134174
2013 Fusion of ZMYND8 and RELA genes in acute erythroid leukemia. PloS one 35 23667654
2022 ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells. Science advances 34 35857506
2010 Xenopus RCOR2 (REST corepressor 2) interacts with ZMYND8, which is involved in neural differentiation. Biochemical and biophysical research communications 33 20331974
2018 The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination. Molecular cell 32 30293785
2020 RACK7 recognizes H3.3G34R mutation to suppress expression of MHC class II complex components and their delivery pathway in pediatric glioblastoma. Science advances 29 32832624
2018 Double duty: ZMYND8 in the DNA damage response and cancer. Cell cycle (Georgetown, Tex.) 26 29393731
2021 ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor-activated cancer. Proceedings of the National Academy of Sciences of the United States of America 24 33593912
2020 ZMYND8 Expression in Breast Cancer Cells Blocks T-Lymphocyte Surveillance to Promote Tumor Growth. Cancer research 21 33148660
2017 Chromatin reader ZMYND8 is a key target of all trans retinoic acid-mediated inhibition of cancer cell proliferation. Biochimica et biophysica acta. Gene regulatory mechanisms 21 28232094
2021 Regulation of ZMYND8 to Treat Cancer. Molecules (Basel, Switzerland) 18 33670804
2021 ZMYND8 promotes the growth and metastasis of hepatocellular carcinoma by promoting HK2-mediated glycolysis. Pathology, research and practice 16 33517164
2021 Aberrant FBXW7-mediated ubiquitination and degradation of ZMYND8 enhances tumor progression and stemness in bladder cancer. Experimental cell research 16 34487730
2017 Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes. The Biochemical journal 15 28432260
2017 The Structure of the ZMYND8/Drebrin Complex Suggests a Cytoplasmic Sequestering Mechanism of ZMYND8 by Drebrin. Structure (London, England : 1993) 14 28966017
2022 ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers. BMC biology 13 36153585
2018 ZMYND8 is a primary HIF coactivator that mediates breast cancer progression. Molecular & cellular oncology 12 30250924
2023 Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance. Clinical cancer research : an official journal of the American Association for Cancer Research 11 36692427
2022 De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations. Genetics in medicine : official journal of the American College of Medical Genetics 11 35916866
2024 USP7 deubiquitinates epigenetic reader ZMYND8 to promote breast cancer cell migration and invasion. The Journal of biological chemistry 8 39128723
2022 ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation. Cell death & disease 7 36064715
2020 A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function. Journal of biosciences 6 31965980
2025 Targeting the histone reader ZMYND8 inhibits antiandrogen-induced neuroendocrine tumor transdifferentiation of prostate cancer. Nature cancer 5 40102673
2025 ZMYND8 drives HER2 antibody resistance in breast cancer via lipid control of IL-27. Nature communications 5 40281007
2025 ZMYND8 Reads H3K36me2 to Activate CEBPE Transcription and Suppress Multiple Myeloma Progression through the Inhibition of Adaptive UPR Pathways. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40347515
2025 ZMYND8 promotes the Warburg effect and tumorigenesis through c-Myc activation in pancreatic cancer. Oncogene 4 40579459
2021 Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma. Journal of cancer research and clinical oncology 4 34462784
2025 The hypoxia-induced chromatin reader ZMYND8 drives HIF-dependent metabolic rewiring in breast cancer. The Journal of biological chemistry 2 40912652
2021 Exploiting a key transcriptional dependency: ZMYND8 and IRF8 in AML. Molecular cell 2 34478652
2025 RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40125808
2024 ZMYND8 Is a Regulator of Sonic Hedgehog Signaling in ATRA-Mediated Differentiation of Neuroblastoma Cells. Biochemistry 1 38804064
2026 The novel retinoid WYC-209 sensitizes multiple myeloma to carfilzomib via epigenetically upregulating ZMYND8. Experimental hematology & oncology 0 41913198
2026 The chromatin reader ZMYND8 recruits the NuRD component GATAD2A through its MYND domain to regulate MAPT213 long noncoding RNA transcription. The Journal of biological chemistry 0 41999894
2025 The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8. Cell & bioscience 0 40223119
2025 RACK7 senses and fine-tunes enhancer activity. iScience 0 40734674
2025 OTUD4-ZMYND8-DDX3X Axis Drives Immunosuppressive Microenvironment in Spinal Metastases of Triple-Negative Breast Cancer. Neoplasia (New York, N.Y.) 0 41297414
2025 MEK inhibitor induces cardiac complications by preventing ZMYND8-mediated ubiquitination and proteasomal degradation of HMGB1. Biochemical pharmacology 0 41423035
2023 Radiosensitization of IDH-Mutated Gliomas through ZMYND8 - a Pathway to Improved Outcomes. Clinical cancer research : an official journal of the American Association for Cancer Research 0 36826993