Affinage

ZMYND8

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

Length
1186 aa
Mass
131.7 kDa
Annotated
2026-06-11
51 papers in source corpus 34 papers cited in narrative 35 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

ZMYND8 is a multivalent chromatin reader that integrates combinatorial histone-mark recognition with transcriptional control at enhancers and DNA damage sites (PMID:27058665, PMID:27926874). Its rigid PHD-BRD-PWWP supramodule reads combinatorial marks including H3K4me1/me0-H3K14ac, H3.1K36me2 and H4K16ac while presenting a charged surface for DNA, and disruption of any single domain collapses the reader network and impairs chromatin recruitment (PMID:27477906, PMID:27926874, PMID:26655721). Through its MYND domain, ZMYND8 binds proline-rich (PPPLΦ) motifs in the NuRD subunit GATAD2A, bridging ZMYND8 to the NuRD remodeling/deacetylation complex; at DNA double-strand breaks this PAR-dependent recruitment enforces transcriptional silencing and promotes homologous-recombination repair, with the requisite chromatin engagement licensed by KDM5A/KDM5C demethylation of H3K4me3 (PMID:25593309, PMID:28572115, PMID:27732854, PMID:41999894). At active and super-enhancers, ZMYND8 acts as a transcriptional 'brake' in complex with KDM5C, restraining H3K4me3/H3K27ac deposition and eRNA output (PMID:27058665). Beyond repression, an oligomerization switch diversifies its output: a coiled-coil homodimer engages CyclinT1/P-TEFb to activate transcription, whereas the monomer engages the CHD4-NuRD repressor, and ZMYND8 cooperates with BRD4 (via reader-cassette binding to the BRD4 ET domain) and HIF-1α/HIF-2α to release paused RNA Pol II at oncogenic and lineage-specific enhancers (PMID:30134174, PMID:34358447, PMID:29629903). ZMYND8 abundance is tuned post-translationally by FBXW7-mediated polyubiquitination and degradation counteracted by USP7 deubiquitination at K1034, and its histone engagement can be competitively sequestered to the cytoplasm by Drebrin binding the PHD-BRD-PWWP module (PMID:34487730, PMID:39128723, PMID:28966017). These activities place ZMYND8 at the center of DNA repair, enhancer regulation, lineage differentiation, and multiple cancer programs including HIF-driven metastasis, cholesterol/27-HC metabolism, and NRF2-dependent antioxidant defense (PMID:29629903, PMID:33932349, PMID:38488001). Rare PWWP and MYND domain missense variants that abolish Drebrin or GATAD2A binding, together with a learning defect on knockdown of the Drosophila ortholog, implicate ZMYND8 in a neurodevelopmental disorder (PMID:35916866).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Low

    An early interaction screen first linked the then-named PRKCBP1 protein to PKCβI signaling, establishing a physical partner before any chromatin role was known.

    Evidence GST pulldown/immunoprecipitation from a cDNA library and Northern expression analysis

    PMID:11003709

    Open questions at the time
    • Single pulldown without functional follow-up
    • No connection to later chromatin-reading function established
  2. 2010 Medium

    The question of whether ZMYND8 acts as a transcriptional repressor was first addressed by linking it to a corepressor partner and a developmental phenotype.

    Evidence Yeast two-hybrid and Co-IP showing RCOR2 interaction, with overexpression in Xenopus embryos blocking neural differentiation

    PMID:20331974

    Open questions at the time
    • Mechanism of repression not defined
    • No chromatin-binding determinants identified
  3. 2015 High

    ZMYND8 was defined as a bromodomain chromatin reader that couples transcriptional repression to DNA repair, answering how active chromatin is silenced and channeled into homologous recombination at breaks.

    Evidence BRD localization screen after DNA damage, reciprocal Co-IP with NuRD, and knockdown with HR repair and transcription assays; separate study mapping histone-mark and RNA Pol II Ser5P binding

    PMID:25593309 PMID:26655721

    Open questions at the time
    • Direct histone-mark code not fully resolved at this stage
    • Recruitment kinetics and PAR dependence not yet established
  4. 2016 High

    The molecular basis of ZMYND8 chromatin targeting and NuRD bridging was resolved, defining the reader code, the GATAD2A interaction, the enhancer-brake function, and the structural supramodule.

    Evidence Histone peptide binding with PHD-Bromo mutagenesis (H3K4me1-H3K14ac), MYND-GATAD2A PPPLΦ binding with laser-damage recruitment, KDM5C complex purification with enhancer ChIP-seq, and crystal structure of the PHD-BRD-PWWP cassette

    PMID:27058665 PMID:27477906 PMID:27732854 PMID:27926874

    Open questions at the time
    • How reader recognition is switched between repressive and activating contexts not resolved
    • Direct DNA-binding contribution to recruitment not quantified
  5. 2017 High

    The chromatin licensing step for damage recruitment was clarified by showing that H3K4me3 demethylation is a prerequisite, and that Drebrin can competitively sequester ZMYND8 to the cytoplasm.

    Evidence KDM5A knockdown with ZMYND8 recruitment and HR assays at DSBs; crystal structure of Drebrin ADF-H/ZMYND8 PHD-BRD-PWWP with competition binding and live-cell localization shift

    PMID:28572115 PMID:28966017

    Open questions at the time
    • Trigger that initiates Drebrin-mediated shuttling in cells unclear
    • Quantitative contribution of cytoplasmic sequestration to nuclear function unknown
  6. 2018 High

    ZMYND8 was shown to switch between repressive and activating outputs through oligomerization and to drive HIF-dependent and immunoglobulin loci programs, explaining its dual transcriptional behavior.

    Evidence Coiled-coil homodimer reconstitution with CyclinT1/P-TEFb vs CHD4-NuRD monomer binding; HIF-1α/2α Co-IP with p300 acetylation site mapping and tumor models; B-cell KO with ChIP-seq at the Igh 3'RR and CSR/SHM assays

    PMID:29629903 PMID:30134174 PMID:30293785

    Open questions at the time
    • What controls the monomer/dimer equilibrium in vivo not defined
    • How acetylation at K1007/K1034 alters complex choice not mechanistically resolved
  7. 2019 Medium

    Post-transcriptional control of ZMYND8 abundance was extended to lncRNA-directed degradation, addressing how its levels are tuned in cancer.

    Evidence RNA pulldown/RIP of lncRNA TROJAN, ZNF592 competition and ubiquitin-proteasome degradation assays with invasion/xenograft readouts in TNBC

    PMID:30854423

    Open questions at the time
    • ZNF592 mechanism of stabilizing ZMYND8 not structurally defined
    • E3 ligase responsible not identified in this study
  8. 2020 High

    ZMYND8 was connected to oncohistone recognition and to genome-stability-linked innate immunity, broadening its role beyond canonical marks.

    Evidence In vitro and ChIP-seq binding to H3.3G34R with CRISPR knock-in correction and MHC class II readouts; ZMYND8 KO with cGAS-STING-NF-κB activation, IFNβ induction and syngeneic/Rag1 KO mouse models

    PMID:32832624 PMID:33148660

    Open questions at the time
    • How G34R alters reader engagement structurally not resolved
    • Link between repair function and micronucleus suppression not mechanistically dissected
  9. 2021 Medium

    Multiple studies positioned ZMYND8 as a regulator of cancer transcriptional and metabolic programs and identified additional partners and degradation control.

    Evidence Co-IP with BRD4 ET domain plus IRF8/MYC enhancer ChIP-seq in AML; phospho-EZH2 (T487) binding with PRC2/FOXM1 readouts; SREBP2/Mediator enhancer-looping with mevalonate KO phenotypes; FBXW7 polyubiquitination of ZMYND8; c-Myc Co-IP with glycolysis assays

    PMID:33593912 PMID:33932349 PMID:34358447 PMID:34487730 PMID:40579459

    Open questions at the time
    • Whether ZMYND8 directly reads phospho-EZH2 or acts via an adaptor unclear
    • Relative contribution of each program across tissues not established
  10. 2022 Medium

    ZMYND8's enhancer repression was placed downstream of ARID1A/CHD4 chromatin context and tied to cholesterol metabolite control and neurodevelopmental genetics.

    Evidence ChIP-seq/Co-IP placing ZMYND8-CHD4 at ARID1A-dependent H3.3/H4K16ac super-enhancers; 27-HC metabolite/LXR analysis in mammary tumor models; yeast two-hybrid domain mapping of patient variants with Drosophila habituation assay

    PMID:35857506 PMID:35916866 PMID:36153585

    Open questions at the time
    • Causality of human ZMYND8 variants in disease not proven by family genetics in this corpus
    • Direct enzymatic control of metabolite genes vs indirect effects not separated
  11. 2024 High

    The stability and antioxidant arms of ZMYND8 regulation were defined, identifying USP7 as the deubiquitinase opposing FBXW7 and an NRF2 feedback loop.

    Evidence USP7 domain-mapped Co-IP and in vitro deubiquitination at K1034 with migration assays; ZMYND8-NRF2 reciprocal Co-IP, ChIP co-recruitment, KEAP1 silencing, NRF2 KO epistasis and ferroptosis readouts

    PMID:38488001 PMID:39128723

    Open questions at the time
    • How USP7 vs FBXW7 balance is set physiologically unknown
    • Mechanism by which ZMYND8 silences KEAP1 not detailed
  12. 2025 High

    ZMYND8 was integrated into lineage transdifferentiation, PRC2-directed H3K27 methylation, enhancer redistribution dynamics, and several additional cancer/metabolic axes, with a chemical probe demonstrating druggability.

    Evidence CRISPR/scRNA-seq, ChIP-seq, SWI/SNF-ZMYND8-FOXM1 Co-IP and iZMYND8-34 inhibition in NEPC; Rack7 conditional KO with PRC2 Co-IP and genome-wide H3K27me3 loss in astrocytes; CUT&RUN tracking of stimulus-driven RACK7 redistribution; PWWP-H3K36me2-CEBPE axis in myeloma; cPLA2α/IL-27 and OTUD4-DDX3X-WNT axes in breast cancer

    PMID:40102673 PMID:40125808 PMID:40281007 PMID:40347515 PMID:40734674 PMID:41297414

    Open questions at the time
    • How ZMYND8 directs PRC2 genomic targeting mechanistically not resolved
    • Whether the activating enhancer redistribution uses the dimeric P-TEFb form not directly linked
  13. 2026 High

    High-resolution structure of the coiled-coil MYND module confirmed homodimeric architecture and defined GATAD2A proline-rich recognition driving locus-specific lncRNA/mRNA balance.

    Evidence Crystal structure of the ZMYND8 coiled-coil MYND domain with quantitative GATAD2A binding, domain mutagenesis, and ChIP for GATAD2A recruitment at MAPT213

    PMID:41999894

    Open questions at the time
    • Generalizability of MAPT-specific recruitment logic to other loci unknown
    • Coupling of dimerization state to GATAD2A vs P-TEFb choice not directly tested here

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether ZMYND8 possesses intrinsic E3 ubiquitin ligase activity, and how its monomer/dimer switch is governed to select repressive vs activating complexes in a given cell context, remain open.
  • Reported HMGB1 E3-ligase-like activity not reconstituted biochemically (idx 29, Low confidence)
  • Upstream signals controlling oligomerization equilibrium undefined
  • Integration of competing PTMs (acetylation, ubiquitination) into output choice unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 5 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 3 R-HSA-4839726 Chromatin organization 2
Partners
BRD4CCNT1CHD4FBXW7GATAD2AHIF1AKDM5CUSP7
Complex memberships
KDM5C complexNuRD complexP-TEFbPRC2

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 ZMYND8 functions as a bromodomain-containing chromatin reader that recruits the NuRD (nucleosome remodeling and histone deacetylation) complex to damaged chromatin, mediating transcriptional repression and promoting repair by homologous recombination at DNA double-strand breaks, particularly within transcriptionally active chromatin. Localization screen of BRD proteins after DNA damage, co-immunoprecipitation, knockdown with DSB repair and transcription assays Genes & development High 25593309
2016 ZMYND8 (RACK7) forms a biochemical complex with the H3K4me3-specific demethylase KDM5C and occupies active enhancers including super-enhancers; loss of RACK7 or KDM5C leads to enhancer overactivation characterized by H3K4me3 and H3K27Ac deposition and increased eRNA and nearby gene transcription, identifying RACK7/KDM5C as an enhancer 'brake'. Biochemical complex purification, ChIP-seq, genetic KO/KD with histone modification and transcription readouts Cell High 27058665
2017 KDM5A demethylates H3K4me3 near DNA double-strand break sites, and this demethylation is required for ZMYND8-NuRD binding to chromatin and recruitment to DNA damage; KDM5A deficiency impairs transcriptional silencing and HR repair. ChIP-seq/ChIP at DSB sites, genetic KD of KDM5A with ZMYND8 recruitment assays, HR repair assays The Journal of cell biology High 28572115
2016 The PHD-Bromodomain cassette of ZMYND8 recognizes the combinatorial histone mark H3K4me1-H3K14ac (and H3K4me0-H3K14ac), mediating its function as a transcriptional corepressor of JARID1D and antagonizing expression of metastasis-linked genes. Histone peptide binding assays, PHD-Bromo domain mutagenesis, ChIP, knockdown with invasion assays in vitro and in vivo Molecular cell High 27477906
2016 The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A; this interaction bridges ZMYND8-NuRD and facilitates rapid, poly(ADP-ribose)-dependent recruitment of GATAD2A/NuRD to DNA damage sites to promote HR. ZMYND8 and NuRD share genome-wide binding at active promoters and enhancers, but ZMYND8 depletion does not globally affect NuRD occupancy. Direct interaction assays (MYND domain with GATAD2A peptides), Co-IP, ChIP-seq, live-cell recruitment assays after laser damage, HR repair assays Cell reports High 27732854
2016 The crystal structure of the ZMYND8 PHD-BRD-PWWP triple reader cassette reveals a rigid structural supramodule capable of simultaneously recognizing multiple histone PTMs while providing a charged platform for DNA binding; disruption of single domains destroys the functional network and impairs recruitment to DNA damage sites. X-ray crystallography of PHD-BRD-PWWP, histone binding assays, single-domain mutagenesis, DNA damage recruitment assays Cell reports High 27926874
2015 ZMYND8 binds the histone marks H3.1K36me2 and H4K16ac through its conserved chromatin-binding modules, shows preference for canonical H3.1 over variant H3.3, and is recruited to ATRA-responsive developmental genes; ZMYND8 interacts with Ser5-phosphorylated RNA polymerase II in a DNA template-dependent manner. In vitro histone-binding assays with domain mutants, ChIP, co-immunoprecipitation with RNA Pol II, ATRA treatment gene expression studies The Journal of biological chemistry Medium 26655721
2018 ZMYND8 interacts with HIF-1α and HIF-2α and enhances elongation of HIF-induced oncogenic genes by recruiting BRD4 and promoting release of paused RNA polymerase II; ZMYND8 acetylation at K1007 and K1034 by p300 is required for HIF activation, breast cancer progression, and metastasis. Co-immunoprecipitation of ZMYND8 with HIF-1α/HIF-2α, p300 acetylation assays, acetylation-site mutagenesis, ChIP for BRD4 and RNA Pol II, mouse tumor/metastasis models The Journal of clinical investigation High 29629903
2018 ZMYND8 forms a homodimer via its coiled-coil domain; the homodimer preferentially associates with CyclinT1 of the P-TEFb complex to activate transcription, while the monomer associates with the CHD4 subunit of the NuRD repressor complex; ZMYND8-P-TEFb interaction promotes ATRA-mediated neuronal differentiation. Biochemical reconstitution of ZMYND8-P-TEFb complex, direct binding assay with CyclinT1, reporter gene assays, ChIP, neuronal differentiation assays with KD Cell reports High 30134174
2018 ZMYND8 controls immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) by binding promoters and super-enhancers including the Igh 3' regulatory region; ZMYND8 deficiency increases 3'RR polymerase loading but decreases acceptor region transcription and CSR. B-cell specific ZMYND8 KO, ChIP-seq for ZMYND8 at Igh enhancers, CSR and SHM functional assays, RNA Pol II ChIP Molecular cell High 30293785
2010 ZMYND8 interacts with RCOR2 (REST corepressor 2) via co-immunoprecipitation; both proteins function as transcriptional repressors and overexpression of ZMYND8 inhibits neural differentiation in Xenopus embryos. Yeast two-hybrid screen, co-immunoprecipitation, overexpression in Xenopus embryos with neural differentiation readout Biochemical and biophysical research communications Medium 20331974
2000 PRKCBP1 (ZMYND8) protein specifically interacts with PKCβI via its carboxy terminus, identified by immunoprecipitation of GST-fused PRKCBP1. GST pulldown/immunoprecipitation using monoclonal antibody screen of cDNA library, Northern analysis for tissue expression Mammalian genome Low 11003709
2017 The crystal structure of the Drebrin ADF-H domain in complex with ZMYND8 PHD-BRD-PWWP reveals that Drebrin competes with modified histones for ZMYND8 binding; Drebrin binding can shuttle ZMYND8 from the nucleus to the cytoplasm, suggesting a cytoplasmic sequestration mechanism. X-ray crystallography of Drebrin ADF-H/ZMYND8 PHD-BRD-PWWP complex, competition binding assays, live-cell imaging showing nuclear-to-cytoplasmic redistribution Structure High 28966017
2020 RACK7 (ZMYND8) recognizes the histone H3.3G34R patient mutation in vitro and in vivo and suppresses transcription of CIITA (master regulator of MHC class II) and genes involved in vesicular transport of MHC class II molecules, resulting in suppression of MHC class II surface expression; CRISPR correction of H3.3G34R reduces RACK7 chromatin binding and derepresses the same genes. In vitro binding assays (RACK7 to H3.3G34R), ChIP-seq in patient-derived glioblastoma cells, CRISPR knock-in correction, RNA-seq, functional MHC class II surface assays Science advances High 32832624
2021 ZMYND8 directly activates IRF8 transcription in AML through lineage-specific enhancers in parallel with MYC; ZMYND8 occupancy at IRF8 and MYC enhancers requires BRD4 via direct binding of ZMYND8's reader cassette to the ET domain of BRD4, and this interaction is required for proper chromatin occupancy and AML cell survival in vitro and in vivo. Co-IP of ZMYND8 with BRD4 ET domain, ChIP-seq in AML cell lines and patient samples, ZMYND8 KO with proliferation/survival readouts in vivo, domain-binding assays Molecular cell High 34358447
2021 ZMYND8 preferentially binds phosphorylated EZH2 (T487, phosphorylated by CDK1); ZMYND8 depletion enhances PRC2-dependent function of EZH2 and suppresses the FOXM1 transcription program; ZMYND8 is required for EZH2-FOXM1 interaction and FOXM1-dependent MMP gene expression and EZH2-mediated cell migration and invasion in VHL-deficient cancer cells. Co-IP showing enhanced ZMYND8-EZH2 binding with T487 phosphorylation, ZMYND8 KD with PRC2 activity, FOXM1 interaction, MMP expression, and migration/invasion readouts Proceedings of the National Academy of Sciences Medium 33593912
2021 ZMYND8 and SREBP2 drive enhancer-promoter interactions to facilitate recruitment of the Mediator complex, upregulating mevalonate pathway genes; this ZMYND8-dependent cholesterol biosynthesis pathway is essential for Lgr5+ intestinal stem cell self-renewal and intestinal tumorigenesis downstream of YAP. ChIP-seq for ZMYND8 and SREBP2, chromatin conformation capture (enhancer-promoter looping), KO of ZMYND8 with mevalonate gene expression, cholesterol measurements, intestinal organoid and tumor model assays Molecular cell High 33932349
2021 FBXW7 E3 ubiquitin ligase interacts directly with ZMYND8 and degrades it via polyubiquitination, thereby controlling ZMYND8 protein levels; low FBXW7 leads to ZMYND8 accumulation and promotes bladder cancer progression and stemness. Bioinformatic interaction prediction, co-immunoprecipitation of FBXW7 with ZMYND8, polyubiquitination assay, functional cell proliferation/migration assays, in vivo tumor model Experimental cell research Medium 34487730
2019 The lncRNA TROJAN binds ZMYND8 and increases its degradation through the ubiquitin-proteasome pathway by repelling ZNF592 from ZMYND8, thereby reducing ZMYND8 protein stability and promoting metastasis-related gene expression in TNBC. RNA pulldown/RIP showing TROJAN-ZMYND8 binding, ubiquitin-proteasome assay for ZMYND8 degradation, ZNF592 competition assays, functional invasion assays, in vivo xenograft Science advances Medium 30854423
2022 ZMYND8 interacts with CHD4 (NuRD) at ARID1A-bound H3.3+ H4K16ac+ super-enhancers to suppress a subset of genes governing extracellular matrix, motility, and EMT; ARID1A is required for CHD4 recruitment to H3.3, and ZMYND8 acts downstream in this pathway. ChIP-seq for ZMYND8, CHD4, ARID1A, H3.3, H4K16ac; Co-IP of ZMYND8 with CHD4; ARID1A KD epistasis experiments; gene expression analysis BMC biology Medium 36153585
2022 ZMYND8 missense variants in the PWWP domain abolish interaction with Drebrin, and missense variants in the MYND domain disrupt interaction with GATAD2A, as established by yeast two-hybrid assays; neuronal knockdown of the Drosophila ZMYND8 ortholog results in decreased habituation learning. Yeast two-hybrid assays with PWWP and MYND domain mutants, Drosophila neuronal KD with habituation learning assay Genetics in medicine Medium 35916866
2020 ZMYND8 inhibits micronucleus formation and DNA damage in breast cancer cells; loss of ZMYND8 triggers activation of the cGAS DNA sensor in micronuclei, activating STING and NF-κB (but not TBK1/IRF3), inducing IFNβ and ISG expression, and promoting CD4+/CD8+ T-cell infiltration and tumor suppression. ZMYND8 KO in breast cancer cells with micronucleus quantification, cGAS/STING pathway activation assays, cytokine measurements, syngeneic mouse model with T-cell depletion antibodies and Rag1 KO mice Cancer research High 33148660
2024 USP7 deubiquitinase directly binds the 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 cell migration and invasion. Co-IP of USP7 with ZMYND8, domain mapping (TRAF/UBL vs PBP), in vitro deubiquitination assay at K1034, KD/OE with migration/invasion readouts, target gene expression analysis The Journal of biological chemistry High 39128723
2022 ZMYND8 is a master transcriptional regulator of 27-hydroxycholesterol metabolism: it increases cholesterol biosynthesis and oxidation while blocking cholesterol efflux and catabolism, leading to 27-HC accumulation in breast cancer stem cells; 27-HC promotes EMT and tumor initiation through liver X receptor activation. ZMYND8 KO/KD in genetic mouse mammary tumor and human breast cancer models, cholesterol/27-HC metabolite measurements, LXR reporter assays, ChIP for ZMYND8 at cholesterol metabolism gene loci Science advances Medium 35857506
2024 ZMYND8 increases NRF2 protein stability through KEAP1 silencing and directly interacts with NRF2 to recruit it to promoters of antioxidant genes; NRF2 in turn directly controls ZMYND8 expression, establishing a positive feedback loop that sustains BCSC antioxidant defense and ferroptosis resistance. Co-IP of ZMYND8 with NRF2, ChIP showing ZMYND8-NRF2 co-recruitment to antioxidant gene promoters, KEAP1 expression analysis after ZMYND8 KO, NRF2 KO epistasis, ROS/ferroptosis assays, mammosphere models The Journal of clinical investigation High 38488001
2025 ZMYND8 enhances cPLA2α expression by inducing c-Myc; cPLA2α inactivates phosphatidylcholine-specific phospholipase C to inhibit diacylglycerol production, thereby diminishing PKC activity and leading to IL-27 secretion that confers trastuzumab/pertuzumab resistance in HER2+ breast cancer. ZMYND8 KO/OE in resistant tumor cells and patient-derived organoids, ChIP for c-Myc at cPLA2α promoter, lipid metabolite measurements, IL-27 secretion assays, patient-derived xenograft models Nature communications Medium 40281007
2025 FOXM1 stabilizes ZMYND8 binding to H3K4me1-H3K14ac chromatin; antiandrogen therapy releases SWI/SNF from androgen receptor, facilitating SWI/SNF interaction with ZMYND8-FOXM1 to upregulate neuroendocrine lineage regulators and drive NEPC transdifferentiation; small molecule iZMYND8-34 inhibiting ZMYND8 histone recognition blocks NEPC development. CRISPR-Cas9 screen combined with scRNA-seq tracking, ChIP-seq for ZMYND8 with H3K4me1-H3K14ac, Co-IP of SWI/SNF with ZMYND8-FOXM1, ZMYND8 KO mouse model, pharmacological inhibition with iZMYND8-34 Nature cancer High 40102673
2025 RACK7 (ZMYND8) interacts with the PRC2 complex and establishes genomic locations of SUZ12 and H3K27 methylation; deletion of Rack7 in astrocytes causes genome-wide decrease of H3K27me3 and aberrant astrocyte development with Wnt signaling overactivation. Rack7 conditional KO mouse model, Co-IP of RACK7 with PRC2 components, ChIP-seq for H3K27me3 and SUZ12 genome-wide, transcriptome analysis, Wnt pathway reporter assays Advanced science High 40125808
2025 RACK7 swiftly redistributes from repressed to activated enhancers in response to acute stimulations in a transcription-dependent manner and positively regulates enhancer activation by promoting RNA polymerase II recruitment. ChIP-seq/CUT&RUN tracking of RACK7 redistribution after acute stimulation, transcription inhibitor experiments, RNA Pol II ChIP iScience Medium 40734674
2025 ZMYND8 acts as an E3 ubiquitin ligase-like factor mediating ubiquitination and proteasomal degradation of HMGB1 in cardiomyocytes; MEK inhibitor trametinib inhibits ZMYND8, leading to aberrant HMGB1 accumulation and cardiomyocyte death. ZMYND8 KO in cardiomyocytes, ubiquitination assays for HMGB1 with ZMYND8 present/absent, HMGB1 stability measurements, trametinib treatment with ZMYND8 activity readouts Biochemical pharmacology Low 41423035
2026 The crystal structure of the ZMYND8 coiled-coil MYND domain reveals a homodimeric architecture; the MYND domain specifically recruits GATAD2A to the MAPT213 internal regulatory region through direct interaction with proline-rich motifs in GATAD2A's central region, suppressing MAPT213 lncRNA transcription while promoting protein-coding MAPT expression. Crystal structure of ZMYND8 coiled-coil MYND domain, Co-IP/direct binding assays of MYND with GATAD2A proline-rich motifs, ChIP for GATAD2A recruitment, quantitative binding measurements, domain mutagenesis The Journal of biological chemistry High 41999894
2021 ZMYND8 directly interacts with c-Myc (confirmed by Co-IP), activating c-Myc transcriptional activity through downstream epigenetic regulatory pathways to promote the Warburg effect and aerobic glycolysis in pancreatic cancer cells. Co-immunoprecipitation of ZMYND8 with c-Myc, CUT&Tag and RNA-seq integration, proteomic profiling, glycolysis assays, in vivo xenograft with c-Myc KD rescue Oncogene Medium 40579459
2025 ZMYND8 PWWP domain reads H3K36me2 and activates CEBPE transcription in an H3K36me2-dependent manner; CEBPE then represses adaptive UPR pathways (ERN1, XBP1, ATF6) to suppress multiple myeloma cell survival. ChIP for ZMYND8 at CEBPE locus with H3K36me2 dependence, Co-IP assays, PWWP domain mutation experiments, RNA-seq and ChIP-seq combined analysis, ZMYND8 KD/KO with UPR pathway and proliferation readouts Advanced science Medium 40347515
2025 Phosphorylated EZH2 T487D (phosphomimic) shows increased binding to ZMYND8, consistent with CDK1 phosphorylation of EZH2 at T487 promoting ZMYND8-EZH2 interaction, as demonstrated independently by phospho-EZH2 pulldown in TNBC cells. Co-IP/pulldown of phosphomimic EZH2 T487D with ZMYND8 in TNBC cells bioRxivpreprint Low
2025 OTUD4 deubiquitinase directly interacts with and stabilizes ZMYND8; ZMYND8 acts as a scaffold promoting assembly of the DDX3X-CK1ε complex, thereby activating WNT/β-catenin signaling; this OTUD4-ZMYND8-DDX3X axis upregulates CSF1 and promotes M2 macrophage polarization in TNBC spinal metastasis. Co-IP of OTUD4 with ZMYND8 and ZMYND8 with DDX3X/CK1ε, ubiquitination/stability assays, WNT/β-catenin reporter, CSF1 expression and macrophage polarization assays, 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 205 25593309
2016 Suppression of Enhancer Overactivation by a RACK7-Histone Demethylase Complex. Cell 156 27058665
2017 Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair. The Journal of cell biology 142 28572115
2018 ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis. The Journal of clinical investigation 141 29629903
2016 ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes. Molecular cell 124 27477906
2019 The endogenous retrovirus-derived long noncoding RNA TROJAN promotes triple-negative breast cancer progression via ZMYND8 degradation. Science advances 102 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 98 27732854
2016 Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin. Cell reports 78 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 64 26655721
2021 ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency. Molecular cell 54 34358447
2024 ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2. The Journal of clinical investigation 50 38488001
2021 The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability. Molecular cell 48 33932349
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 37 23667654
2022 ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells. Science advances 36 35857506
2010 Xenopus RCOR2 (REST corepressor 2) interacts with ZMYND8, which is involved in neural differentiation. Biochemical and biophysical research communications 34 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.) 29 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
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 22 28232094
2020 ZMYND8 Expression in Breast Cancer Cells Blocks T-Lymphocyte Surveillance to Promote Tumor Growth. Cancer research 21 33148660
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 16 28432260
2022 ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers. BMC biology 15 36153585
2017 The Structure of the ZMYND8/Drebrin Complex Suggests a Cytoplasmic Sequestering Mechanism of ZMYND8 by Drebrin. Structure (London, England : 1993) 14 28966017
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 12 36692427
2018 ZMYND8 is a primary HIF coactivator that mediates breast cancer progression. Molecular & cellular oncology 12 30250924
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 10 39128723
2025 ZMYND8 drives HER2 antibody resistance in breast cancer via lipid control of IL-27. Nature communications 8 40281007
2022 ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation. Cell death & disease 8 36064715
2025 Targeting the histone reader ZMYND8 inhibits antiandrogen-induced neuroendocrine tumor transdifferentiation of prostate cancer. Nature cancer 7 40102673
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 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) 5 40347515
2025 ZMYND8 promotes the Warburg effect and tumorigenesis through c-Myc activation in pancreatic cancer. Oncogene 5 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 3 40912652
2024 ZMYND8 Is a Regulator of Sonic Hedgehog Signaling in ATRA-Mediated Differentiation of Neuroblastoma Cells. Biochemistry 2 38804064
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
2025 The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8. Cell & bioscience 1 40223119
2025 RACK7 senses and fine-tunes enhancer activity. iScience 1 40734674
2025 MEK inhibitor induces cardiac complications by preventing ZMYND8-mediated ubiquitination and proteasomal degradation of HMGB1. Biochemical pharmacology 1 41423035
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 OTUD4-ZMYND8-DDX3X Axis Drives Immunosuppressive Microenvironment in Spinal Metastases of Triple-Negative Breast Cancer. Neoplasia (New York, N.Y.) 0 41297414
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

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