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Showing ZMYND11 — BS69 is a alias.

ZMYND11

Zinc finger MYND domain-containing protein 11 · UniProt Q15326

Length
602 aa
Mass
71.0 kDa
Annotated
2026-06-11
60 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/10 claims corpus-supported (90%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZMYND11 (BS69/BRAM1) is a multidomain chromatin reader that couples a specific histone modification state to transcriptional repression, co-transcriptional splicing, and tumor suppression (PMID:24590075, PMID:25263594). Through a tandem PHD-bromo-PWWP module it selectively recognizes H3K36me3 deposited on the histone variant H3.3, with H3.3 specificity enforced by encapsulation of the H3.3-unique Ser31 residue in a composite pocket formed across the bromo and PWWP domains (PMID:24590075). At H3.3K36me3-marked gene bodies and promoters ZMYND11 acts as a transcriptional co-repressor, restraining RNA Pol II elongation, supporting Pol II pausing, and sustaining proper transcription initiation; its loss reduces the Pol II pausing index and disrupts H3.3/H3K36me3 occupancy at target genes (PMID:24590075, PMID:42262664). The same H3K36me3-dependent chromatin engagement directs a splicing function: ZMYND11 associates with U5 snRNP components including EFTUD2 and promotes intron retention by antagonizing EFTUD2, and it governs a brain-specific RBFOX2-dependent isoform switch (PMID:25263594, PMID:41068108). A second functional surface is the C-terminal coiled-coil-MYND module, which homodimerizes and recruits binding partners through PXLXP motifs or arginine-methylation marks: it binds the co-repressor N-CoR and the cellular repressors MGA, c-Myb, and ETS2, the methyl-mark on R194 of HNRNPA1, and the histone methyltransferase KMT2A, and it is also the docking site for viral oncoproteins (adenovirus E1A, EBV EBNA2 and LMP1) (PMID:10734313, PMID:11733528, PMID:11244510, PMID:26845565, PMID:28119415, PMID:39341825, PMID:41279818). In the nucleus ZMYND11 forms complexes with p53 and p400 and associates with the p21Cip1 promoter through p53 to restrain the p53-p21Cip1 senescence pathway (PMID:17721438). ZMYND11 protein abundance is set by competing modifications — PIAS1-enhanced SUMOylation, MAGE-C2/HCA587-driven ubiquitin-proteasomal degradation, and USP53-mediated deubiquitination and stabilization (PMID:19766626, PMID:24866244, PMID:39044157). A distinct cytoplasmic splice isoform, BRAM1, binds the BMP type IA receptor through its MYND domain and inhibits BMPR-IA activation of Smad signaling (PMID:9663660, PMID:30324105). Loss of ZMYND11 in neurons and neural progenitors derepresses non-neuronal and latent developmental gene programs and impairs neurogenesis, a defect linked to KMT2A inhibition and to Epha2/PI3K signaling, and a ZRSID-associated point mutation abolishes the ZMYND11-KMT2A interaction (PMID:41279818, PMID:41068108, PMID:40281637). The oncogenic ZMYND11-MBTD1 fusion subverts these activities by stably incorporating into the NuA4/TIP60 acetyltransferase complex and mislocalizing it to ZMYND11-bound gene bodies and cis-regulatory elements, driving aberrant acetylation and MYC-driven self-renewal in leukemogenesis, dependent on both the TIP60 interaction and the H3K36me3-binding PWWP domain (PMID:33594072, PMID:35705031).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1995 High

    Established ZMYND11/BS69 as a binding partner and functional antagonist of a viral oncoprotein, the first clue to its role in transcriptional control.

    Evidence Yeast two-hybrid, reciprocal co-IP, and reporter assay with adenovirus E1A in transformed cells

    PMID:7621829

    Open questions at the time
    • No endogenous cellular function identified
    • Binding domain on BS69 not yet mapped
    • Mechanism of transactivation inhibition unknown
  2. 2000 Medium

    Defined a molecular basis for repression by showing the MYND domain recruits the co-repressor N-CoR, framing BS69 as a transcriptional co-repressor.

    Evidence Co-IP, domain deletion, and reporter repression assay

    PMID:10734313

    Open questions at the time
    • Endogenous target genes not identified
    • Single lab
    • Link to chromatin not established
  3. 1998 Medium

    Revealed isoform-dependent compartmentalization: a cytoplasmic splice form (BRAM1) binds BMPR-IA, expanding the gene's reach beyond the nucleus.

    Evidence Yeast two-hybrid, co-IP, and fractionation/imaging in mammalian cells

    PMID:9663660

    Open questions at the time
    • Functional consequence for BMP signaling not yet tested
    • Single lab
    • Regulation of isoform choice unknown
  4. 2001 High

    Identified the PXLXP motif as the common code recognized by the MYND domain, unifying viral (EBNA2) and cellular (MGA) partner recognition and explaining competition between them.

    Evidence Co-IP, GST pull-down, and PXLXP motif mutagenesis

    PMID:11244510 PMID:11733528

    Open questions at the time
    • Structural basis of PXLXP recognition not resolved
    • Functional output of MGA/c-Myb repression in vivo unclear
  5. 2002 Medium

    Showed that the cytoplasmic BRAM1 isoform and MYND domain also intercept viral signaling, dampening LMP1- and TNF-driven NF-kB activation.

    Evidence Pull-down, co-IP, confocal, and NF-kB reporter assays

    PMID:12181323

    Open questions at the time
    • Direct biochemical target in the IkBa pathway not defined
    • Single lab
    • Physiological relevance untested
  6. 2006 Medium

    Placed full-length BS69 on chromatin and mitotic chromosomes in association with remodelers, deacetylases and methyltransferases, anchoring its function to chromatin regulation.

    Evidence Endogenous chromatin fractionation, co-IP, immunofluorescence

    PMID:16565076

    Open questions at the time
    • Histone mark recognized not yet identified
    • Direct vs indirect chromatin association unresolved
    • Specific complexes not purified
  7. 2006 High

    Demonstrated adaptor function in viral signaling by bridging LMP1 to TRAF6 to selectively drive JNK activation, distinct from TNF signaling.

    Evidence Co-IP, siRNA knockdown, chimeric rescue, lipid raft fractionation, JNK assay

    PMID:16382137

    Open questions at the time
    • How a chromatin reader operates at membrane rafts mechanistically unclear
    • Relevance to nuclear function unconnected
  8. 2007 High

    Connected BS69 to senescence control, showing it forms p53/p400 complexes and restrains the p53-p21Cip1 pathway, an endogenous tumor-suppressive axis.

    Evidence RNAi, senescence markers, co-IP, ChIP on p21 promoter, double-knockdown epistasis

    PMID:17721438

    Open questions at the time
    • Whether chromatin-reading is required for p53 regulation untested
    • Mechanism of p21 promoter repression not detailed
  9. 2009 Medium

    Defined post-translational control of BS69 abundance and localization via PIAS1-enhanced SUMOylation through a PHD-dependent mechanism.

    Evidence Co-IP, SUMO modification assay, domain mutagenesis, differentiation reporter

    PMID:19766626

    Open questions at the time
    • SUMO acceptor sites not mapped
    • Functional consequence of SUMOylation for chromatin binding unclear
    • Single lab
  10. 2009 Medium

    Extended viral signaling roles, showing BS69 can both negatively regulate LMP1-NF-kB (via TRADD) and positively regulate antiviral TLR3-TICAM-1 signaling through nuclear-to-cytoplasmic translocation.

    Evidence Co-IP, siRNA, confocal translocation, NF-kB/IFN-b reporter and cytokine assays

    PMID:19379743 PMID:19795416

    Open questions at the time
    • Signals triggering nucleocytoplasmic shuttling not defined
    • Reconciliation of opposing NF-kB outcomes unclear
    • Single labs
  11. 2013 Medium

    Resolved the MYND domain fold (bba cross-brace zinc topology) and showed partner binding requires distinct flanking charged residues, defining a binding mode distinct from AML1/ETO.

    Evidence NMR of related MYND, homology modeling and mutagenesis of BS69 MYND, NMR titration

    PMID:23372760

    Open questions at the time
    • BS69 MYND not directly solved by NMR
    • Quantitative affinities not measured
    • Single lab
  12. 2014 High

    Defined the central molecular function: ZMYND11 reads H3.3K36me3 via PWWP with H3.3-Ser31-dependent specificity from the tandem bromo-PWWP, co-localizes with H3K36me3 in gene bodies, and represses transcription at the Pol II elongation step.

    Evidence Crystal structure of bromo-PWWP with H3.3K36me3 peptide, ChIP-seq, Pol II elongation and tumor-growth assays

    PMID:24590075

    Open questions at the time
    • Mechanism by which reading restrains elongation not fully detailed
    • Effector recruited at elongation step not defined
  13. 2014 High

    Linked H3.3K36me3 reading to co-transcriptional splicing, showing ZMYND11 associates with U5 snRNP/EFTUD2 and promotes intron retention by antagonizing EFTUD2 in a chromatin-dependent manner.

    Evidence Pull-down, co-IP, RNA-seq, ChIP, and KD+EFTUD2-overexpression epistasis

    PMID:25263594

    Open questions at the time
    • Direct EFTUD2 antagonism mechanism not structurally resolved
    • Scope of regulated splicing events incomplete
  14. 2014 Medium

    Identified an additional layer of abundance control: MAGE-C2/HCA587 promotes ZMYND11 ubiquitination and proteasomal degradation, with functional loss reflected in increased LMP1-driven IL-6.

    Evidence MS, co-IP, GST pull-down, ubiquitination assay, siRNA, IL-6 readout

    PMID:24866244

    Open questions at the time
    • E3 ligase responsible not identified
    • Ubiquitination sites not mapped
    • Single lab
  15. 2016 High

    Explained MYND-mediated partner recognition architecturally: the CC-MYND module homodimerizes to engage two PXLXP motifs of EBNA2 with avidity, and this engagement inhibits EBNA2 transactivation and LCL proliferation.

    Evidence Crystal structure, ITC, ChIP, reporter and proliferation assays, mutagenesis

    PMID:26845565

    Open questions at the time
    • Whether the same dimeric avidity applies to cellular partners untested at structural level
  16. 2017 Medium

    Showed selective co-repression of ETS2 (not ETS1) explains divergent tumor-suppressive versus oncogenic outcomes at shared ETS binding sites, suppressing a migration program.

    Evidence Co-IP, deletion mapping, ChIP-seq cistrome comparison, reporter and migration assays

    PMID:28119415

    Open questions at the time
    • Structural basis of ETS2 selectivity unknown
    • Single lab
    • In vivo relevance untested
  17. 2018 Medium

    Established a conserved cytoplasmic mechanism in vivo: the MYND domain binds the Bmpr1a kinase domain to block Smad1/5/8 activation, with cytoplasmic Mga antagonizing this to tune BMP-dependent cell fate.

    Evidence Zebrafish CRISPR/TALEN loss-of-function, co-IP, Smad phosphorylation assay, domain mapping

    PMID:30324105

    Open questions at the time
    • Conservation to mammalian BMP signaling not directly shown
    • Single lab
    • Isoform (BRAM1) contribution in vivo not delineated
  18. 2019 High

    Refined the host-restriction model, showing type 2 EBNA2 carries a third PXLXP motif binding an extra CC-MYND dimer, and that increased ZMYND11 association restricts EBNA2 function.

    Evidence Pull-down, SAXS, mutagenesis, B-cell growth and gene expression assays

    PMID:31283782

    Open questions at the time
    • High-resolution structure of the trimeric assembly lacking
    • Quantitative cellular ZMYND11 stoichiometry unknown
  19. 2021 High

    Defined the leukemogenic mechanism of the ZMYND11-MBTD1 fusion: it recruits NuA4/TIP60 to pro-leukemic cis-regulatory elements, sustaining active acetylated chromatin, and requires both TIP60 interaction and the PWWP H3K36me3-reading domain.

    Evidence Murine HSPC transformation, in vivo AML model, ChIP-seq, systematic domain mutagenesis, co-IP, bromodomain inhibitor

    PMID:33594072

    Open questions at the time
    • How fusion converts repressive reading into activation mechanistically incomplete
    • Therapeutic window not defined
  20. 2022 High

    Showed the fusion stably integrates into endogenous NuA4/TIP60 and mislocalizes it to ZMYND11-occupied gene bodies, driving MYC-centered acetylation, transcription, splicing changes, and HSPC self-renewal.

    Evidence Complex purification, ChIP-seq, RNA-seq, splicing analysis, ESC differentiation and self-renewal assays

    PMID:35705031

    Open questions at the time
    • Direct MYC regulatory element causality not isolated
    • Single lab
  21. 2024 Medium

    Identified an arginine-methyl reading function: the MYND domain binds R194-methylated HNRNPA1 to retain it in the nucleus, restrain stress granule formation, and counter HNRNPA1-driven PKM2/PKM1 shift, disrupted by PRMT5 inhibition.

    Evidence Co-IP, MYND mutagenesis, stress granule imaging, PKM ratio assay, PRMT5 inhibitor, tumor formation assay

    PMID:39341825

    Open questions at the time
    • Structural basis of methyl-arginine recognition by MYND not solved
    • Single lab
    • In vivo relevance of metabolic shift untested
  22. 2024 Medium

    Completed the abundance-control circuit by identifying USP53 as a deubiquitinase that stabilizes ZMYND11, partly mediating USP53 anti-tumor effects in breast cancer.

    Evidence Co-IP, ubiquitination assay, domain deletion, gain/loss rescue, xenograft

    PMID:39044157

    Open questions at the time
    • Ubiquitin chain type removed not characterized
    • Counterbalancing E3 in this context not identified
    • Single lab
  23. 2025 Medium

    Connected ZMYND11 to neurodevelopmental disease mechanism: loss derepresses non-neuronal programs via failure to inhibit KMT2A, impairs dendritic morphology, and a ZRSID point mutation abolishes the KMT2A interaction, with revumenib attenuating the phenotype.

    Evidence Neuronal conditional knockout, co-IP, disease-variant mutagenesis, KMT2A inhibition, morphology, RNA-seq (preprint)

    PMID:41279818

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct vs indirect KMT2A inhibition mechanism unresolved
    • Genotype-phenotype scope across ZRSID variants limited
  24. 2025 Medium

    Defined neurodevelopmental and neurogenic roles, showing ZMYND11 controls progenitor/neuron production through a brain-specific RBFOX2-dependent isoform switch and through Epha2/PI3K signaling coupled to H3K36me3 and Pol II occupancy.

    Evidence hPSC cortical differentiation, mouse KO, RNA-seq, splicing analysis, ChIP (H3K36me3, Pol II), Epha2 rescue, neurogenesis assays

    PMID:40281637 PMID:41068108

    Open questions at the time
    • Direct targets of the RBFOX2 isoform switch not enumerated
    • Mechanism linking H3K36me3 gain to Pol II loss at Epha2 unclear
    • Two independent models, single labs each
  25. 2026 High

    Provided a structural and genomic refinement: crystal structures of WH, PHD, and CC-MYND domains reveal redox/pH-sensitive oligomerization and nucleic-acid/histone binding cooperation, and ZMYND11 robustly occupies promoters where its loss reduces Pol II pausing and H3.3/H3K36me3, with a new ALKBH6 interaction.

    Evidence Crystal structures, ITC, mutagenesis, co-IP (ALKBH6); CUT&Tag, ChIP-seq, pausing index, RNA-seq, ROS and proliferation assays

    PMID:41591843 PMID:42262664

    Open questions at the time
    • Functional role of ALKBH6 interaction not established
    • Physiological relevance of redox-sensitive oligomerization unclear
    • How promoter occupancy reconciles with elongation control incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZMYND11's H3.3K36me3 reading is mechanistically converted into Pol II pausing/elongation control versus the activation imposed by the ZMYND11-MBTD1 fusion, and how its many partner interactions are coordinated in time and space, remain unresolved.
  • No structural model of ZMYND11 engaging Pol II or pausing machinery
  • Effector linking reading to repression at elongation undefined
  • Integration of nuclear chromatin reading with cytoplasmic signaling roles unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0042393 histone binding 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
EBNA2EFTUD2ETS2HNRNPA1KMT2ALMP1MGAUSP53
Complex memberships
NuA4/TIP60 acetyltransferase complex (via ZMYND11-MBTD1 fusion)U5 snRNP/spliceosomep53-p400 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 BS69/ZMYND11 specifically interacts with adenovirus 5 E1A (289R) protein, requiring the region unique to the large E1A protein for high-affinity binding, and co-immunoprecipitates with E1A in adenovirus-transformed 293 cells; BS69 specifically inhibits transactivation by the 289R E1A protein but not the 243R E1A protein. Yeast two-hybrid, co-immunoprecipitation, reporter gene transcription assay The EMBO journal High 7621829
2000 BS69/ZMYND11 represses transcription at least in part through interaction with the co-repressor N-CoR; this interaction is mediated by the MYND domain in the BS69 C-terminus. Expression of E1A inhibits BS69-mediated repression. Co-immunoprecipitation, reporter gene transcription assay, domain deletion analysis Oncogene Medium 10734313
1998 BRAM1, an alternatively spliced form of BS69/ZMYND11, localizes to the cytoplasm (whereas BS69 is nuclear) and specifically binds the BMP type IA receptor (BMPR-IA); the C-terminal half of BRAM1 is sufficient for BMPR-IA binding. Yeast two-hybrid, co-immunoprecipitation, subcellular localization by cell fractionation/imaging Genes to cells Medium 9663660
2001 The C-terminal MYND domain of BS69/ZMYND11 binds the Epstein-Barr virus oncoprotein EBNA2 and the Myc-related cellular protein MGA through a common PXLXP motif present in all three binding partners; viral proteins compete with MGA for BS69 binding in a PXLXP-dependent manner. Co-immunoprecipitation, GST pull-down, mutagenesis of PXLXP motif The Journal of biological chemistry High 11733528
2001 BS69/ZMYND11 interacts with the carboxy-terminal negative regulatory domain of c-Myb and inhibits c-Myb transcriptional activity in a dose-dependent manner; the 289R E1A protein can inhibit BS69-mediated repression of c-Myb; direct in vitro interaction between BS69 and c-Myb was demonstrated. Yeast two-hybrid, in vitro binding, reporter gene assay, domain mapping Oncogene Medium 11244510
2002 BRAM1 associates with EBV LMP1 (via the MYND domain of BRAM1 and the CTAR2 region of LMP1) both in vitro and in vivo, and interferes with LMP1-mediated NF-κB activation; BRAM1 also interferes with TNF-α-induced NF-κB activation by targeting IκBα molecules. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, confocal microscopy, reporter gene assay The Journal of biological chemistry Medium 12181323
2005 EMSY binds directly to BS69/ZMYND11 via a conserved motif adjacent to its ENT domain; the crystal structure of EMSY residues 1–108 shows the HP1β/BS69-binding motif in an extended peptide conformation; HP1β chromoshadow domain (CSD) forms a complex with EMSY. Crystal structure (2.0 Å), NMR, biophysical analysis (ITC/analytical ultracentrifugation) EMBO reports Medium 15947784
2005 BS69/ZMYND11 inhibits ubiquitination of adenovirus E1A protein and stabilizes E1A in vivo; this inhibition requires the MYND domain, which mediates E1A binding; BS69 mutants lacking the MYND domain cannot bind E1A and cannot inhibit its ubiquitination. In vivo ubiquitination assay, co-immunoprecipitation, domain deletion mutagenesis Biochemical and biophysical research communications Medium 16300738
2006 BS69/ZMYND11 is a specific adaptor bridging EBV LMP1 and TRAF6 in the LMP1-induced JNK pathway; the MYND domain and a separate region of BS69 bind LMP1 and TRAF6 C-termini, respectively; LMP1 promotes BS69-TRAF6 complex formation; a fraction of LMP1 and BS69 co-localizes in membrane lipid rafts; knockdown of BS69 specifically inhibits LMP1-induced JNK activation but not TNF-α-induced JNK activation. Co-immunoprecipitation, siRNA knockdown, chimeric protein overexpression, lipid raft fractionation, JNK activation assay Molecular and cellular biology High 16382137
2006 Full-length BS69/ZMYND11 is a nuclear protein that associates with chromatin and mitotic chromosomes; it interacts with chromatin remodeling factors including ATP-dependent helicases, histone deacetylases, and histone methyltransferases, as well as the E2F6 transcription factor. Endogenous antibody-based chromatin fractionation, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry Medium 16565076
2007 BS69/ZMYND11 knockdown in primary human fibroblasts induces premature senescence via the p53-p21Cip1 pathway; BS69 forms complexes with both p53 and p400, and associates with the p21Cip1 promoter through p53; knockdown of p53 or p21Cip1, but not p16INK4a or Rb, rescues premature senescence induced by BS69 knockdown. RNA interference knockdown, senescence marker assays (SA-β-gal, SAHF), co-immunoprecipitation, chromatin immunoprecipitation, epistasis by double knockdown EMBO reports High 17721438
2009 BS69/ZMYND11 negatively regulates LMP1-mediated NF-κB activation; BS69 manipulation decreases complex formation between LMP1 and TRADD, thus dampening IκBα degradation and IL-6 upregulation. Co-immunoprecipitation, siRNA-mediated knockdown, NF-κB reporter assay, IL-6 mRNA measurement FEBS letters Medium 19379743
2009 BS69/ZMYND11 is SUMOylated; it interacts with SUMO E3 ligase PIAS1 and the SUMO E2 enzyme Ubc9 through distinct regions, and PIAS1 significantly enhances BS69 SUMO modification; the PHD domain is required for BS69 localization, sumoylation, and inhibitory function in muscle and neuronal differentiation. Co-immunoprecipitation, SUMO modification assay, domain deletion mutagenesis, differentiation reporter assay Experimental cell research Medium 19766626
2009 BS69/ZMYND11 translocates from the nucleus to the cytoplasm upon dsRNA stimulation or TICAM-1 overexpression, is recruited to TICAM-1 signaling speckles, and positively regulates NF-κB/IRF-3 activation and IFN-β production downstream of TLR3-TICAM-1; knockdown of BS69 reduces IFN-β induction. Yeast two-hybrid, co-immunoprecipitation, confocal microscopy, siRNA knockdown, cytokine induction assay European journal of immunology Medium 19795416
2010 BS69/ZMYND11 directly interacts with LMP1/CTAR1 domain and with TRAF3 (a negative regulator of NF-κB); BS69 and TRAF3 cooperate to suppress LMP1/CTAR1-mediated NF-κB activation and IL-6 production; siRNA knockdown of TRAF3 impairs BS69-mediated suppression. Co-immunoprecipitation, siRNA knockdown, NF-κB reporter assay, IL-6 measurement FEBS letters Medium 20138174
2013 The BS69 MYND domain adopts a ββα fold with tandem zinc-binding sites in a cross-brace topology (characterized by homology modeling and mutational analysis); interactions of BS69 MYND with viral and cellular binding partners require distinct charged residues flanking the predicted MYND domain fold, suggesting a different binding mode from AML1/ETO. NMR structure determination (DEAF-1 MYND), homology modeling plus mutational analysis (BS69 MYND), NMR titration mapping PloS one Medium 23372760
2014 ZMYND11 specifically recognizes H3K36me3 on the histone variant H3.3 (H3.3K36me3) via its PWWP domain aromatic cage; H3.3-specific recognition additionally requires encapsulation of the H3.3-specific Ser31 residue in a composite pocket formed by the tandem bromo-PWWP domains. ZMYND11 co-localizes genome-wide with H3K36me3 and H3.3 in gene bodies and its chromatin occupancy requires pre-deposited H3.3K36me3. ZMYND11 functions as a transcription co-repressor by modulating RNA Pol II at the elongation stage. Crystal structure (bromo-PWWP-H3.3K36me3 peptide complex), ChIP-seq, RNA Pol II elongation assay, loss-of-function with tumor growth readout Nature High 24590075
2014 BS69/ZMYND11 selectively recognizes H3.3K36me3 via its chromatin-binding PHD-BROMO-PWWP domains; it associates with U5 snRNP components of the spliceosome including EFTUD2; BS69 promotes intron retention by antagonizing EFTUD2 through physical interaction; this splicing regulatory function depends on BS69 binding to H3K36me3-decorated chromatin. Biochemical pulldown, co-immunoprecipitation, RNA-seq, genetic epistasis (BS69 KD + EFTUD2 overexpression), ChIP Molecular cell High 25263594
2014 The cancer-testis antigen HCA587/MAGE-C2 interacts with BS69/ZMYND11 and promotes its ubiquitination and proteasomal degradation; knockdown of endogenous HCA587 increases BS69 protein levels; HCA587 overexpression enhances LMP1-induced IL-6 production consistent with loss of BS69 function. Mass spectrometry identification, co-immunoprecipitation, GST pull-down, ubiquitination assay, siRNA knockdown, IL-6 measurement Biochemical and biophysical research communications Medium 24866244
2016 The C-terminal coiled-coil-MYND (CC-MYND) domains of BS69/ZMYND11 form a homodimer via coiled-coil self-association, which brings two MYND domains in close proximity to synergistically bind two PXLXP motifs in EBNA2 (CR7 and CR8); ectopic BS69 CC-MYND is recruited to viral promoters via EBNA2, inhibits EBNA2-mediated transactivation, and impairs lymphoblastoid cell line proliferation; MYND domain mutations that abolish EBNA2 binding also abolish inhibitory activity. Crystal structure, ITC, chromatin immunoprecipitation, reporter assay, cell proliferation assay, site-directed mutagenesis PLoS pathogens High 26845565
2017 ZMYND11 interacts with ETS2 (but not ETS1) through the ETS2 N-terminus and acts as a co-repressor to attenuate ETS2-mediated transcriptional activation, enabling ETS2 to suppress a cell migration gene expression program; this specific interaction accounts for the opposing functions of ETS1 (oncogenic) and ETS2 (tumor suppressive) at shared genomic binding sites. Co-immunoprecipitation, deletion mapping, ChIP-seq cistrome comparison, reporter gene assay, cell migration assay Nucleic acids research Medium 28119415
2018 In zebrafish, the MYND domain of Bs69/Zmynd11 binds the kinase domain of Bmpr1a and interferes with Bmpr1a phosphorylation and activation of Smad1/5/8; cytoplasmic Mga antagonizes Bs69 by disrupting the Bs69-Bmpr1a association, thereby facilitating BMP signaling for ventral tailfin cell fate specification. TALEN/CRISPR-Cas9 loss-of-function, co-immunoprecipitation, phosphorylation assay (Smad1/5/8), domain mapping Frontiers in cell and developmental biology Medium 30324105
2019 Type 2 EBV EBNA2 contains a third conserved PXLXP motif absent in type 1 EBNA2, enabling it to bind an additional BS69 CC-MYND molecule; SAXS shows three BS69 CC-MYND dimers bound to two molecules of type 2 EBNA2 TAD; mutation of the third BS69-binding motif in type 2 EBNA2 improves B-cell growth and transcriptional activation, indicating that increased BS69 association restricts type 2 EBNA2 function. Pull-down, SAXS (low-resolution structure), molecular weight analysis, mutagenesis, B-cell growth assay, gene expression assay PLoS pathogens High 31283782
2021 The ZMYND11-MBTD1 (ZM) fusion protein recruits the NuA4/TIP60 histone acetyltransferase complex to cis-regulatory elements of pro-leukemic genes (Hoxa, Meis1, Myb, Myc, Sox4), sustaining active chromatin enriched in histone acetylation and devoid of repressive marks; both the TIP60 interaction and the H3K36me3-binding PWWP domain of ZMYND11 are required for ZM oncogenic function. Murine hematopoietic stem/progenitor cell transformation assay, in vivo AML model, ChIP-seq, systematic domain mutagenesis, co-immunoprecipitation, bromodomain inhibitor treatment Nature communications High 33594072
2022 ZMYND11-MBTD1 fusion is stably incorporated into the endogenous NuA4/TIP60 complex, leading to its mislocalization to gene bodies normally occupied by ZMYND11; this causes increased chromatin acetylation and altered transcription (notably at the MYC oncogene) and alternative splicing; ZMYND11-MBTD1 favors MYC-driven pluripotency and self-renewal of hematopoietic stem/progenitor cells. Biochemical complex purification, ChIP-seq, RNA-seq, alternative splicing analysis, embryonic stem cell differentiation assay, hematopoietic progenitor self-renewal assay Cell reports High 35705031
2024 ZMYND11 binds arginine-194-methylated HNRNPA1 via its MYND domain, retaining HNRNPA1 in the nucleus and preventing stress granule formation in the cytoplasm; ZMYND11 counteracts HNRNPA1-driven increase in the PKM2/PKM1 ratio; PRMT5 inhibition disrupts ZMYND11 recognition of methylated HNRNPA1. Co-immunoprecipitation, domain mutagenesis (MYND), stress granule imaging, PKM2/PKM1 ratio assay, PRMT5 inhibitor treatment, in vitro tumor formation assay Signal transduction and targeted therapy Medium 39341825
2024 USP53 deubiquitylase interacts with ZMYND11 and catalyzes its deubiquitination and stabilization; the USP53 Cys-box domain (aa 33-50) is required for enzyme activity but not for ZMYND11 binding; USP53 anti-tumor effects in breast cancer cells are partially mediated through ZMYND11. Co-immunoprecipitation, ubiquitination assay, domain deletion analysis, gain/loss-of-function rescue experiments, xenograft model Biological procedures online Medium 39044157
2025 ZMYND11 deficiency in mouse neurons causes aberrant upregulation of non-neuronal gene programs leading to reduced dendritic branching and spine density; ZMYND11 interacts with and inhibits histone methyltransferase KMT2A (MLL1); a ZRSID-associated ZMYND11 point mutation abolishes KMT2A interaction; gene expression changes from ZMYND11 loss are attenuated by KMT2A inhibitor revumenib. Neuronal-specific conditional knockout, co-immunoprecipitation, point mutagenesis, pharmacological KMT2A inhibition (revumenib), dendritic morphology assay, RNA-seq bioRxivpreprint Medium 41279818
2025 ZMYND11 deficiency in cortical neural stem cells upregulates latent developmental pathways impairing progenitor and neuron production; beyond chromatin, ZMYND11 controls a brain-specific RNA isoform switch involving the splicing regulator RBFOX2. Human pluripotent stem cell cortical differentiation model, ZMYND11 loss-of-function, RNA-seq, splicing isoform analysis Nature communications Medium 41068108
2025 Zmynd11 deficiency decreases Epha2 expression and disrupts PI3K signaling; under Zmynd11 deficiency, H3K36me3 modification on the Epha2 promoter abnormally increases while RNA Pol II binding decreases; restoration of PI3K signaling via exogenous Epha2 rescues aberrant neurogenesis caused by Zmynd11 depletion in vitro and in vivo. Mouse knockout model, ChIP (H3K36me3, Pol II), Epha2 rescue overexpression, neurosphere/neurogenesis assay Cell & bioscience Medium 40281637
2026 Crystal structures of ZMYND11 winged helix (WH), PHD, and coiled-coil-MYND (CC-MYND) domains reveal intermolecular zinc finger bonds in the PHD domain and intermolecular disulfide bonds in the CC domain; oligomeric state of PHD is pH-dependent and redox state of CC impairs binding; Bromo-PWWP domains cooperate with the WH domain and PHD domain to bind nucleic acids and histones respectively; both PHD and CC-MYND domains interact with nucleic acid repair protein ALKBH6. Crystal structure determination, ITC, mutagenesis, co-immunoprecipitation (ALKBH6 interaction) Nucleic acids research High 41591843
2026 Using CUT&Tag, ZMYND11 was found to robustly occupy promoter regions (not only gene bodies) in mouse ESCs and MEFs, with occupancy positively correlating with gene expression and Pol II occupancy; ZMYND11 deficiency reduces the Pol II pausing index, H3.3 occupancy, and H3K36me3 at genes, indicating impaired transcription initiation; ZMYND11 knockout induces transcriptomic changes, impairs cell proliferation, and aberrantly activates 2-cell-specific transcriptional programs via ROS accumulation. CUT&Tag, ChIP-seq comparison, Pol II pausing index analysis, RNA-seq, cell proliferation assay, ROS measurement FASEB journal Medium 42262664

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature 267 24590075
2014 BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing. Molecular cell 186 25263594
1995 BS69, a novel adenovirus E1A-associated protein that inhibits E1A transactivation. The EMBO journal 80 7621829
2001 The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif. The Journal of biological chemistry 79 11733528
2000 The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR. Oncogene 70 10734313
2001 BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb. Oncogene 53 11244510
1998 BRAM1, a BMP receptor-associated molecule involved in BMP signalling. Genes to cells : devoted to molecular & cellular mechanisms 44 9663660
2006 BS69, a specific adaptor in the latent membrane protein 1-mediated c-Jun N-terminal kinase pathway. Molecular and cellular biology 39 16382137
2021 ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism. Nature communications 36 33594072
2014 A de novo mutation in ZMYND11, a candidate gene for 10p15.3 deletion syndrome, is associated with syndromic intellectual disability. European journal of medical genetics 28 25281490
2006 New insights into BS69 functions. The Journal of biological chemistry 28 16565076
2005 Binding of EMSY to HP1beta: implications for recruitment of HP1beta and BS69. EMBO reports 27 15947784
2017 Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2. Nucleic acids research 25 28119415
2017 Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome. Journal of applied genetics 25 28933030
2020 ZMYND11-related syndromic intellectual disability: 16 patients delineating and expanding the phenotypic spectrum. Human mutation 24 32097528
2017 Downregulation of ZMYND11 induced by miR-196a-5p promotes the progression and growth of GBM. Biochemical and biophysical research communications 24 29066350
2016 BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2. PLoS pathogens 23 26845565
2016 A de novo missense mutation in ZMYND11 is associated with global developmental delay, seizures, and hypotonia. Cold Spring Harbor molecular case studies 23 27626064
2013 Structural and functional analysis of the DEAF-1 and BS69 MYND domains. PloS one 22 23372760
2009 BS69 negatively regulates the canonical NF-kappaB activation induced by Epstein-Barr virus-derived LMP1. FEBS letters 22 19379743
2016 Chicken gga-miR-19a Targets ZMYND11 and Plays an Important Role in Host Defense against Mycoplasma gallisepticum (HS Strain) Infection. Frontiers in cellular and infection microbiology 21 27683641
2019 Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity. PLoS pathogens 20 31283782
2020 Hsa_circ_0008225 inhibits tumorigenesis of glioma via sponging miR-890 and promoting ZMYND11 expression. Journal of pharmacological sciences 19 32192854
2015 Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion. Genes, chromosomes & cancer 19 26608508
2021 MicroRNA-196a promotes renal cancer cell migration and invasion by targeting BRAM1 to regulate SMAD and MAPK signaling pathways. International journal of biological sciences 17 34803496
2019 Gga-miR-19b-3p Inhibits Newcastle Disease Virus Replication by Suppressing Inflammatory Response via Targeting RNF11 and ZMYND11. Frontiers in microbiology 16 31507581
2002 Negative regulation of Epstein-Barr virus latent membrane protein 1-mediated functions by the bone morphogenetic protein receptor IA-binding protein, BRAM1. The Journal of biological chemistry 15 12181323
2024 Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity. Signal transduction and targeted therapy 14 39341825
2010 BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappaB activation. FEBS letters 14 20138174
2007 BS69, a corepressor interacting with ZHX1, is a bifunctional transcription factor. Frontiers in bioscience : a journal and virtual library 14 17127430
2007 BS69 is involved in cellular senescence through the p53-p21Cip1 pathway. EMBO reports 13 17721438
2021 ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder. Clinical genetics 12 34216016
2009 BS69 undergoes SUMO modification and plays an inhibitory role in muscle and neuronal differentiation. Experimental cell research 12 19766626
2014 Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its degradation in the ubiquitin-proteasome pathway. Biochemical and biophysical research communications 11 24866244
2005 Ubiquitin-dependent degradation of adenovirus E1A protein is inhibited by BS69. Biochemical and biophysical research communications 11 16300738
2022 Oncogenic ZMYND11-MBTD1 fusion protein anchors the NuA4/TIP60 histone acetyltransferase complex to the coding region of active genes. Cell reports 10 35705031
2024 USP53 Affects the Proliferation and Apoptosis of Breast Cancer Cells by Regulating the Ubiquitination Level of ZMYND11. Biological procedures online 8 39044157
2010 Analysis of copy number variations of BS69 in multiple types of hematological malignancies. Annals of hematology 8 20425112
2009 Oligomerized TICAM-1 (TRIF) in the cytoplasm recruits nuclear BS69 to enhance NF-kappaB activation and type I IFN induction. European journal of immunology 8 19795416
2018 Mga Modulates Bmpr1a Activity by Antagonizing Bs69 in Zebrafish. Frontiers in cell and developmental biology 7 30324105
2018 The Transcriptional Repressor BS69 is a Conserved Target of the E1A Proteins from Several Human Adenovirus Species. Viruses 7 30469473
2021 Intragenic Deletion of the ZMYND11 Gene in 10p15.3 is Associated with Developmental Delay Phenotype: A Case Report. Cytogenetic and genome research 6 34818214
2020 MicroRNA-196b promotes cell growth and metastasis of ovarian cancer by targeting ZMYND11. Minerva medica 5 32512976
2019 Regulation of BS69 Expression in Cancers. Anticancer research 5 31262855
2010 The MYND domain-containing protein BRAM1 inhibits lymphotoxin beta receptor-mediated signaling through affecting receptor oligomerization. Cellular signalling 5 20732415
2006 Molecular cloning, expression and characterization of the zebrafish bram1 gene, a BMP receptor-associated molecule. Journal of biomedical science 5 16456708
2024 Further Delineation of Clinical Phenotype of ZMYND11 Variants in Patients with Neurodevelopmental Dysmorphic Syndrome. Genes 4 38397245
2025 ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis. Nature communications 3 41068108
2024 Probing the biological consequences of a previously undescribed de novo mutation of ZMYND11 in a schizophrenia patient by CRISPR genome editing and induced pluripotent stem cell based in vitro disease-modeling. Schizophrenia research 3 38290943
2023 Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of neurological disorders-associated gene Zmynd11 prior to onset of motor symptoms. microPublication biology 3 37008727
2024 Acute myeloid leukemia with a ZMYND11::MBTD1 fusion gene following chemotherapy and radiotherapy for breast cancer: A case report. Leukemia research reports 2 39258225
2014 The putative tumor suppressor ZMYND11 recognizes H3.3K36me3. Cancer discovery 2 24795016
2025 Zmynd11 is essential for neurogenesis by coordinating H3K36me3 modification of Epha2 and PI3K signaling pathway. Cell & bioscience 1 40281637
2024 ZMYND11 Functions in Bimodal Regulation of Latent Genes and Brain-like Splicing to Safeguard Corticogenesis. bioRxiv : the preprint server for biology 1 39464123
2026 Novel intermolecular zinc fingers and redox-driven conformational changes dictate tumor suppressor ZMYND11's role in cooperative recognition of diverse targets. Nucleic acids research 0 41591843
2026 A Complex Neurodevelopmental Phenotype Resembling a Chromatinopathy With Concurrent 7p Duplication and 10p Deletion Involving ZMYND11: A Case Report and Literature Review. Molecular genetics & genomic medicine 0 42003802
2026 H3.3K36me3 Reader ZMYND11 Localizes to Gene Promoter and Regulates Transcription Initiation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 42262664
2025 ETS2 targets ZMYND11 to inhibit thyroid cancer progression via the mTOR signaling pathway. PloS one 0 40938895
2025 ZMYND11 Restrains KMT2A to Enable a Neuronal Developmental Program. bioRxiv : the preprint server for biology 0 41279818
2025 ZMYND11::MBTD1 Fusion in Myeloid/NK Cell Precursor Leukemia: A Case Report With Literature Review and Diagnostic Implications. Pediatric blood & cancer 0 41454826

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