Affinage

KAT6A

Histone acetyltransferase KAT6A · UniProt Q92794

Length
2004 aa
Mass
225.0 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KAT6A (MOZ/MYST3) is a MYST-family lysine acetyltransferase that functions as the catalytic subunit of a tetrameric complex with BRPF1/2/3, ING5, and EAF6 to acetylate histone H3 (at K9, K14, and K23) and non-histone substrates including p53, SMAD3, and COP1, thereby regulating transcription of developmental genes, hematopoietic stem cell maintenance programs, and senescence pathways (PMID:18794358, PMID:16702405, PMID:25772242, PMID:33995658). KAT6A is recruited to unmethylated CpG island-containing promoters via N-terminal winged helix domains that bind CpG-rich DNA and nucleosomal dyad sequences, and to acetylated chromatin via tandem PHD fingers that recognize H3K14ac, establishing a feed-forward loop for H3K9/K23 acetylation at target loci such as HOXA9, Meis1, and Tbx1 (PMID:36537216, PMID:36754959, PMID:22713874, PMID:22921202). KAT6A-deposited H3K9ac is read by the YEATS-domain protein ENL to promote transcriptional elongation in AML, and oncogenic fusions (MOZ-TIF2, MOZ-CBP) drive leukemogenesis by aberrantly recruiting CBP/p300 to CpG-rich developmental gene promoters and conferring self-renewal to committed progenitors (PMID:34853079, PMID:12676584, PMID:15607963, PMID:32997997). KAT6A suppresses cellular senescence by maintaining H3K9ac and H3K27ac at loci encoding INK4A-ARF pathway inhibitors, and its loss in the nervous system impairs synaptic plasticity and Wnt signaling through transcriptional downregulation of Rspo2 (PMID:25772242, PMID:24307508, PMID:38758792).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Establishing that MOZ possesses intrinsic HAT activity and dual transcriptional regulatory domains resolved whether this MYST-family protein was a bona fide acetyltransferase with direct transcriptional function.

    Evidence In vitro HAT assay and transcriptional reporter assays in yeast

    PMID:11313971

    Open questions at the time
    • Histone substrate specificity (which lysines) not yet determined
    • No in vivo chromatin context tested
  2. 2001 High

    Discovery that MOZ physically associates with RUNX1/AML1 and coactivates RUNX1-dependent transcription identified MOZ as a transcriptional cofactor for a master hematopoietic regulator, linking its enzymatic activity to myeloid gene programs.

    Evidence Co-immunoprecipitation, in vitro HAT assay, reporter assay, myeloid differentiation experiments

    PMID:11742995 PMID:11965546

    Open questions at the time
    • Whether MOZ coactivation requires HAT activity versus transactivation domain was unresolved
    • Direct genomic targets of the MOZ-RUNX1 complex not mapped
  3. 2003 High

    Demonstrating that MOZ-TIF2 requires the MOZ nucleosome-recognition motif and TIF2-mediated CBP recruitment—but not MOZ HAT activity—for leukemic transformation revealed that the oncogenic fusion co-opts CBP/p300 rather than relying solely on MOZ catalytic activity.

    Evidence Murine bone marrow transplant AML model with systematic domain deletion mutants

    PMID:12676584

    Open questions at the time
    • Whether endogenous MOZ HAT activity contributes to fusion-driven leukemia was later shown to be essential
    • Downstream gene targets of MOZ-TIF2 not yet identified
  4. 2004 High

    Genetic studies in zebrafish established that MOZ is required for maintenance of Hox gene expression and segmental identity, with pharmacological HDAC inhibition rescuing the phenotype, connecting MOZ HAT activity to a core developmental patterning program.

    Evidence Positional cloning, morpholino knockdown, TSA rescue, in situ hybridization in zebrafish

    PMID:15128673 PMID:16774997

    Open questions at the time
    • Whether MOZ directly occupies Hox loci was not yet shown by ChIP
    • Mammalian validation pending
  5. 2006 High

    MOZ knockout mice revealed an essential, non-redundant requirement for MOZ in hematopoietic stem cell maintenance and identified PU.1 as a direct interaction partner, placing MOZ at the apex of hematopoietic transcriptional hierarchies.

    Evidence MOZ-null mice, transplantation assay, co-immunoprecipitation, microarray, flow cytometry

    PMID:16702405

    Open questions at the time
    • Whether HSC loss reflects senescence, apoptosis, or differentiation was unclear
    • Direct genomic occupancy of MOZ in HSCs not mapped
  6. 2008 High

    Biochemical reconstitution of the MOZ tetrameric complex (with BRPF1/2/3, ING5, EAF6) demonstrated that complex assembly drastically stimulates nucleosomal H3 acetyltransferase activity, defining the minimal functional unit and identifying BRPF1 as a critical scaffold.

    Evidence Reconstituted complex, in vitro nucleosomal HAT assay, deletion mapping, co-immunoprecipitation

    PMID:18794358

    Open questions at the time
    • Substrate lysine specificity on nucleosomal H3 not resolved in this study
    • In vivo requirement for each subunit not yet tested
  7. 2008 High

    Identification of p53 as a MOZ interaction partner and demonstration that MOZ is required for p53-dependent p21 induction and G1 arrest after DNA damage expanded MOZ function beyond histone acetylation to non-histone substrate acetylation and tumor suppression.

    Evidence Co-immunoprecipitation, MOZ-null MEFs, cell-cycle analysis, reporter assays

    PMID:19001415 PMID:23431171

    Open questions at the time
    • Relative contribution of histone versus p53 acetylation to cell-cycle arrest was not separated
    • Regulation of MOZ activity by signaling pathways was only partially explored
  8. 2012 High

    Crystal and NMR structures of the MOZ tandem PHD fingers bound to H3K14ac-containing peptides revealed how MOZ reads its own product mark, establishing a chromatin-targeting feed-forward mechanism for localization at HOXA9 and other loci.

    Evidence X-ray crystallography (1.47 Å), NMR, fluorescence spectroscopy, ChIP, RT-PCR

    PMID:22713874 PMID:23063713

    Open questions at the time
    • Whether PHD-mediated recruitment is sufficient or requires additional DNA-binding domains was unknown
    • Genome-wide occupancy of PHD mutants not tested
  9. 2012 High

    Linking MOZ to Tbx1 regulation and demonstrating that MOZ loss phenocopies DiGeorge syndrome established MOZ as a direct epigenetic regulator of cardiac and pharyngeal development, with genetic rescue confirming Tbx1 as a critical downstream target.

    Evidence ChIP at Tbx1 locus, Moz mutant mice, Tbx1 transgene rescue, compound heterozygote analysis

    PMID:22921202

    Open questions at the time
    • Whether MOZ regulates Tbx1 through H3K9ac specifically was not dissected
    • Broader set of cardiac target genes not defined
  10. 2015 High

    Demonstration that MOZ suppresses senescence by maintaining H3K9ac and H3K27ac at INK4A-ARF pathway inhibitor loci (Cdc6, Ezh2, Melk) unified the catalytic and anti-senescence functions, explaining why HAT-dead MOZ phenocopies loss-of-function for stem cell self-renewal.

    Evidence MOZ-deficient MEFs, ChIP at target loci, Ink4a-Arf genetic rescue, gene expression profiling

    PMID:24307508 PMID:25772242

    Open questions at the time
    • Whether H3K9ac or H3K27ac (or both) is the critical mark at these loci was not separated
    • Contribution of MOZ-mediated acetylation versus recruitment of other HATs not excluded
  11. 2017 High

    Identification of H3K23 as a key KAT6A substrate mark that recruits the reader protein TRIM24 to activate PIK3CA transcription established a specific writer-reader axis linking KAT6A to PI3K/AKT oncogenic signaling.

    Evidence ChIP, H3K23ac-specific antibody, HAT-mutant and TRIM24 reader-mutant rescue, in vivo xenograft

    PMID:29021135

    Open questions at the time
    • Relative contribution of H3K23ac versus H3K9ac to MOZ target gene activation not globally assessed
    • Whether TRIM24 is the sole effector reader was unknown
  12. 2018 High

    Development of potent, selective KAT6A/B inhibitors (WM-8014, WM-1119) that compete with acetyl-CoA validated KAT6A catalytic activity as a druggable node, inducing INK4A/ARF-dependent senescence and arresting lymphoma in vivo without DNA damage.

    Evidence Biochemical inhibition, structural studies, senescence and DNA damage assays, in vivo lymphoma model

    PMID:30069049

    Open questions at the time
    • Selectivity for KAT6A versus KAT6B in vivo not fully resolved
    • Long-term therapeutic window and resistance mechanisms not explored
  13. 2022 High

    CRISPR screens and ChIP-seq defined a transcriptional control module in AML where KAT6A-deposited H3K9ac is read by the YEATS-domain protein ENL to promote transcriptional elongation, establishing the downstream effector mechanism linking KAT6A catalysis to leukemic gene expression.

    Evidence CRISPR screen, ChIP-seq (H3K9ac, ENL), co-immunoprecipitation, in vivo AML models

    PMID:34853079 PMID:35947126

    Open questions at the time
    • Whether ENL reading of H3K9ac is the dominant mechanism versus TRIM24 reading of H3K23ac at overlapping loci
    • Structural basis of ENL-H3K9ac selectivity at MOZ target promoters not detailed
  14. 2023 High

    Cryo-EM and functional studies revealed that two N-terminal winged helix domains target KAT6A to unmethylated CpG islands by binding CpG-rich linker DNA (WH1) and the nucleosome dyad (WH2), establishing the primary genomic targeting mechanism independent of histone marks.

    Evidence Cryo-EM, NMR, mass spectrometry, ChIP-seq, mutagenesis

    PMID:36537216 PMID:36754959

    Open questions at the time
    • Relative contributions of WH-DNA binding versus PHD-histone binding in determining genome-wide occupancy not fully dissected
    • How CpG methylation dynamics regulate KAT6A redistribution during differentiation unknown
  15. 2024 High

    KAT6A deficiency in hippocampal CA3 neurons impairs synaptic plasticity and memory through loss of Rspo2 transcription and Wnt signaling, extending KAT6A function beyond hematopoiesis and development into neural circuit-level cognition.

    Evidence Conditional KAT6A KO mice, viral RSPO2 rescue, electrophysiology, behavioral assays

    PMID:38758792

    Open questions at the time
    • Whether KAT6A regulates Rspo2 via H3K23ac or H3K9ac not specified
    • Broader neuronal gene targets of KAT6A not mapped genome-wide
  16. 2024 High

    Discovery that MOZ-TIF2 catalyzes histone H3K23 propionylation at developmental gene loci expanded the enzymatic repertoire of KAT6A beyond acetylation to broader acylation, raising questions about the functional distinction between acetylation and propionylation marks.

    Evidence Pharmacological inhibition, dTAG protein degradation, ChIP-seq for H3K23pr, gene expression profiling

    PMID:38889153

    Open questions at the time
    • Whether H3K23pr is a physiological mark of wild-type KAT6A or specific to the fusion context
    • Reader proteins for H3K23pr not identified
    • Relative contributions of acetylation versus propionylation to gene activation unknown
  17. 2025 High

    Identification of KAT6A as a chromatin co-dependency of NUP98 fusion oncoproteins revealed that KAT6A/BRPF1 associate with NUP98 fusions on chromatin and within condensates, with combined KAT6A and menin inhibition showing synergistic anti-leukemic activity.

    Evidence Co-immunoprecipitation, ChIP-seq (H3K23ac), CRISPR screen, pharmacological inhibition, xenograft model

    PMID:40536430

    Open questions at the time
    • Whether KAT6A is recruited by NUP98 fusions directly or via shared chromatin context
    • Mechanism of condensate-mediated KAT6A enrichment at fusion target loci not structurally resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KAT6A selects between acetylation and propionylation substrates, the relative contributions of H3K9ac versus H3K23ac to distinct gene programs, and the complete set of non-histone substrates remain unresolved.
  • Acyl-CoA selectivity mechanism not structurally or biochemically defined
  • No genome-wide separation of H3K9ac-dependent versus H3K23ac-dependent KAT6A target genes
  • Comprehensive non-histone substrate inventory lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1643685 Disease 6 R-HSA-4839726 Chromatin organization 6 R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 3 GO:0005654 nucleoplasm 2
Partners
BRPF1EAF6ENLING5PU.1RUNX1TP53TRIM24
Complex memberships
MOZ-BRPF1-ING5-EAF6MOZ-BRPF2-ING5-EAF6MOZ-BRPF3-ING5-EAF6

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MOZ (KAT6A) has intrinsic histone acetyltransferase (HAT) activity, and additionally possesses a transcriptional repression domain at its N-terminus and a transcriptional activation domain at its C-terminus capable of activating transcription in yeast. In vitro HAT assay, transcriptional reporter assays in yeast Oncogene High 11313971
2001 MOZ is part of the AML1 (RUNX1) transcriptional complex, strongly stimulates AML1-mediated transcription via a transactivation domain (independent of HAT activity), and can acetylate AML1 in vitro. The AML1-MOZ complex increases during M1 myeloid cell differentiation into monocytes/macrophages. Co-immunoprecipitation, in vitro HAT assay, reporter assay, differentiation experiments The EMBO journal High 11742995
2002 MOZ physically and functionally interacts with the Runt-domain transcription factor Runx2 (Cbfa1) and with Runx1 (AML1) via its C-terminal SM domain, potentiating Runx2-dependent transcriptional activation without acetylating Runx2. GST pulldown, co-immunoprecipitation, reporter assays Oncogene Medium 11965546
2003 MOZ activates the MIP-1alpha promoter in a manner largely dependent on a proximal RUNX1 binding site, and co-expression of MOZ and RUNX1 synergistically activates the MIP-1alpha promoter; endogenous RUNX1 is constitutively bound to the MIP-1alpha promoter. Reporter assay, chromatin immunoprecipitation (ChIP), site-directed mutagenesis Nucleic acids research Medium 12771199
2003 MOZ-TIF2-induced AML requires the C2HC nucleosome recognition motif of MOZ (essential for transformation) and TIF2-mediated recruitment of CBP via the CBP interaction domain; MOZ HAT activity is dispensable for transformation. Murine bone marrow transplant AML model, in vitro transformation assay, deletion mutant analysis Cancer cell High 12676584
2004 Zebrafish moz (KAT6A ortholog) is required for maintenance of Hox gene expression (hox1–4) in pharyngeal arches and for specifying segmental identity; homeosis and defective Hox gene expression in moz mutants is rescued by inhibiting histone deacetylase activity with trichostatin A, indicating that MOZ's HAT activity is functionally required. Positional cloning, morpholino knockdown, pharmacological rescue (TSA), in situ hybridization Development (Cambridge, England) High 15128673
2004 MOZ-TIF2 (but not BCR-ABL) confers leukemic stem cell properties including serial replating and AML induction to committed myeloid progenitors (CMP and GMP) that normally lack self-renewal capacity. Flow-sorted progenitor transduction, serial methylcellulose replating, in vivo transplantation Cancer cell High 15607963
2005 MOZ-TIF2 acts as a dominant inhibitor of CBP-dependent transcriptional activators (nuclear receptors, p53) by directly interacting with CBP in vivo (shown by co-IP and FRET); this requires the CBP-binding domain (AD1) of TIF2. MOZ-TIF2 also displays aberrant nuclear distribution and reduces cellular CBP levels, depleting CBP from PML bodies. Co-immunoprecipitation, FRET, reporter assay, immunofluorescence microscopy Molecular and cellular biology High 15657427
2006 MOZ is required for maintenance of hematopoietic stem cells; MOZ-null mice show severe reduction of HSCs, lineage-committed progenitors, and B-lineage cells, and MOZ-deficient fetal liver cells cannot reconstitute hematopoiesis. MOZ interacts with PU.1 and activates PU.1-dependent transcription, with expression of c-Mpl, HoxA9, and c-Kit downregulated in MOZ-null cells. MOZ knockout mice, transplantation assay, co-immunoprecipitation, microarray, flow cytometry Genes & development High 16702405
2006 Zebrafish moz functions cell-intrinsically in cranial neural crest (CNC) cells to specify fate maps of the facial skeleton via Hox-dependent mechanisms; tissue mosaic experiments show Moz and Hox function in CNC but not ectoderm or endoderm. Moz specifies second-segment fate by regulating CNC interaction with the first endodermal pouch. Zebrafish moz mutants, tissue mosaic/chimera experiments, laser ablation, fate mapping Development (Cambridge, England) High 16774997
2007 MOZ interacts directly with the p65 subunit of NF-κB (shown by co-immunoprecipitation and GST pulldown) and enhances expression of NF-κB-dependent promoters; transcriptional activity requires MOZ's C-terminal domain. Co-immunoprecipitation, GST pulldown, reporter assay Experimental hematology Medium 17920756
2008 MOZ forms tetrameric complexes with ING5, EAF6, and BRPF1/2/3; BRPF proteins bridge the association of MOZ with ING5 and EAF6. The acetyltransferase domain of MOZ is sufficient for BRPF1 interaction. Complex formation with BRPF1 and ING5 drastically stimulates MOZ acetyltransferase activity toward nucleosomal histone H3 and free H3/H4. An 18-residue C-terminal 'activation lid' of the catalytic domain is required for BRPF1 interaction. Complex reconstitution, deletion mapping, in vitro HAT assay with nucleosomes, co-immunoprecipitation Molecular and cellular biology High 18794358
2008 MOZ forms a complex with p53 to induce p21 expression and G1 cell-cycle arrest in response to DNA damage; MOZ-/- MEFs fail to arrest in G1 after DNA damage and show impaired p21 induction. The leukemia-associated MOZ-CBP fusion protein inhibits p53-mediated transcription. A tumor-associated p53 mutant (G279E) disrupts the p53-MOZ interaction without affecting p53 DNA binding. Co-immunoprecipitation, MOZ-/- MEFs, cell-cycle analysis (FACS), reporter assays The Journal of biological chemistry High 19001415
2009 BRPF1, as a subunit of the MOZ HAT complex, is required for maintenance of Hox gene expression and proper craniofacial and caudal skeletal patterning in medaka fish; MOZ-deficient mice also show abnormal craniofacial and cervical skeletal patterning with decreased Hox transcripts. Medaka mutant (bis), MOZ-deficient mice, in situ hybridization Developmental biology High 19254709
2010 MOZ-TIF2 and MOZ-CBP interact with transcription factor PU.1 to upregulate CSF1R expression, and PU.1 is essential for MOZ-TIF2 to establish and maintain AML stem cells. AML can be cured by ablating CSF1Rhigh cells in this model. Co-immunoprecipitation, PU.1-deficient mice, CSF1R-promoter suicide transgene, CSF1R inhibitors Nature medicine High 20418886
2011 The first PHD finger of BRPF2 (a scaffold subunit of MOZ complexes) specifically recognizes the unmodified N-terminal tail of histone H3; structural analysis reveals the binding mode, and histone PTMs (H3R2me2as, H3K4me, H3K4ac, H3T3ph) antagonize the interaction. PHD1-mediated histone binding is required for BRPF2 localization to the HOXA9 locus in vivo. NMR solution structure, ITC, fluorescence spectroscopy, mutagenesis, ChIP The Journal of biological chemistry High 21880731
2012 The tandem PHD fingers (PHD12) of MOZ recognize unmodified H3R2 together with acetylated H3K14; crystal structure of PHD12–H3K14ac complex at 1.47 Å resolution reveals the structural basis. PHD12 facilitates MOZ localization to the HOXA9 promoter, promoting H3 acetylation and upregulation of HOXA9 mRNA. NMR (free state), X-ray crystallography (1.47 Å crystal structure with peptide), ChIP, RT-PCR Genes & development High 22713874
2012 The tandem PHD1/2 fingers of MORF (and the equivalent domain of MOZ) bind the N-terminal tail of histone H3, and acetylation of H3K9 or H3K14 enhances binding 2–3 fold; trimethylation of H3K4 inhibits interaction. Both PHD fingers are required for binding to H3K14ac in vivo and for chromatin localization. H3K14ac interaction may promote HAT enzymatic activity in trans. NMR, fluorescence spectroscopy, mutagenesis, fluorescence microscopy, co-immunoprecipitation, in vitro HAT assay Journal of molecular biology High 23063713
2012 MOZ is required for expression of Tbx1 and for H3K9 acetylation at the Tbx1 locus; the MOZ complex occupies the Tbx1 locus in vivo. Lack of MOZ phenocopies DiGeorge syndrome, and heterozygous MOZ mutation combined with Tbx1 haploinsufficiency produces DiGeorge-like anomalies; a Tbx1 transgene rescues the heart phenotype in Moz mutants. ChIP, Moz mutant mice, genetic rescue (Tbx1 transgene), compound heterozygote analysis Developmental cell High 22921202
2013 MOZ is an acetyltransferase of p53 at K120 and K382; MOZ colocalizes with p53 in PML nuclear bodies following cellular stress. The MOZ-PML-p53 ternary complex enhances MOZ-mediated p53 acetylation. Akt phosphorylates MOZ at T369, negatively regulating MOZ-PML complex formation; PML-mediated Akt suppression increases PML-MOZ interaction and induces p53-dependent premature senescence via p21 upregulation. In vitro HAT assay, co-immunoprecipitation, colocalization (immunofluorescence), site-directed mutagenesis, Akt kinase assay Proceedings of the National Academy of Sciences of the United States of America High 23431171
2013 BRPF1 is required for leukemogenesis by MOZ-TIF2; MOZ-TIF2 forms a stable complex with BRPF1, and both co-occupy HOX gene loci by ChIP. BRPF1 depletion decreases MOZ localization at HOX genes and abolishes transformation by MOZ-TIF2. HAT-inactive MOZ-TIF2 cannot deregulate HOX genes or initiate leukemia. Co-immunoprecipitation, ChIP, shRNA knockdown, in vitro and in vivo transformation assays, HAT domain mutation International journal of hematology High 24258712
2014 MOZ HAT activity is required to repress p16(INK4a) expression in hematopoietic and neural stem/progenitor cells; absence of MOZ HAT activity upregulates p16(INK4a), inducing premature senescence. Genetic deletion of p16(INK4a) reverses the proliferative defect in both cell types. MOZ HAT-domain mutant mice, genetic rescue on Ink4a-/- background, colony-forming assay, senescence assay Stem cells (Dayton, Ohio) High 24307508
2014 MOZ is required for germinal center B-cell progression: MOZ-deficient GC B cells are impaired in generating dark zone centroblasts, show decreased cell-cycle progression and BCL-6 expression, with increased differentiation toward IgM and low-affinity IgG1+ memory B cells. Stage-specific Cre-mediated deletion of MOZ, flow cytometry, cell-cycle analysis Proceedings of the National Academy of Sciences of the United States of America High 24979783
2015 MOZ is a potent inhibitor of cellular senescence through the INK4A-ARF pathway, independently of DNA damage signaling. MOZ occupies the Cdc6, Ezh2, and Melk loci and is required to maintain normal H3K9 and H3K27 acetylation at their transcriptional start sites and normal mRNA levels; these genes encode known inhibitors of the INK4A-ARF pathway. MOZ-deficient primary MEFs, ChIP (H3K9ac, H3K27ac at target loci), Ink4a-Arf genetic rescue, gene expression profiling Oncogene High 25772242
2015 MOZ maintains Hox gene expression during embryogenesis and plays opposing roles to BMI1: MOZ promotes and BMI1 represses Hox genes during the shift from repressed to active chromatin state. Homeotic transformations in single Moz and Bmi1 mutants are rescued to wild-type identity in Moz;Bmi1 double knockouts, establishing MOZ and BMI1 as antagonistic chromatin regulators at Hox loci. ES cell genetic models, Moz;Bmi1 double knockout mice, gene expression profiling, skeletal analysis Proceedings of the National Academy of Sciences of the United States of America High 25922517
2016 KAT6A (MOZ) is essential for classically defined adult hematopoietic stem cells: conditional deletion leads to rapid loss of HSC populations (LSK-CD48-CD150+ and LSK-CD34-Flt3-) and quiescent (G0) cells, without affecting steady-state blood production or mouse viability. Conditional (inducible) Moz knockout mice, transplantation assay, flow cytometry, clonal analysis Blood High 27663673
2016 KAT6A maintains permissive histone H3K9 acetylation at the Cd8 locus, sustaining Cd8α transcription and surface CD8 co-receptor expression on T cells during clonal expansion; KAT6A-deficient CD8+ T cells downregulate surface CD8, which reduces TCR signaling and accelerates contraction of the effector-like memory compartment. Conditional KAT6A KO, ChIP (H3K9ac at Cd8 locus), flow cytometry, infection model Cell reports High 27653692
2016 MYST3 (KAT6A) binds the proximal promoter region of the ESR1 (ERα) gene via its HAT domain, and HAT-inactivating mutations abolish ERα promoter activation; KAT6A depletion profoundly reduces ERα expression in ER+ breast cancer cells. ChIP, HAT domain point mutants, shRNA knockdown, reporter assay Oncogene Medium 27893709
2017 KAT6A acetylates histone H3 at lysine 23 (H3K23), and this mark recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, enhancing PI3K/AKT signaling. KAT6A acetyltransferase-deficient mutants and TRIM24 mutants lacking H3K23ac-binding sites fail to promote PIK3CA expression or AKT phosphorylation. ChIP, reporter assay, H3K23ac-specific antibody, HAT-mutant rescue, in vivo xenograft, pan-PI3K inhibitor rescue Cancer research High 29021135
2018 Highly potent and selective KAT6A/B inhibitors WM-8014 and WM-1119 are reversible competitors of acetyl-CoA and inhibit MYST-catalysed histone acetylation; structural studies confirm the inhibitor binding mode. These compounds induce cell-cycle exit and INK4A/ARF-dependent cellular senescence without causing DNA damage, and arrest lymphoma progression in mice. Biochemical inhibition assay, structural studies, cellular senescence assay, DNA damage assay, in vivo lymphoma model Nature High 30069049
2019 Src family kinase HCK activity is required for HCMV reactivation; HCK signaling recruits MOZ histone acetyltransferase to the viral major immediate-early promoter, promoting histone acetylation after ERK-mediated histone phosphorylation, thus driving viral gene expression specifically in dendritic cells. Differential phosphoproteomics, pharmacological and genetic inhibition of HCK and MOZ, ChIP at viral promoter The Journal of biological chemistry Medium 31273084
2020 MOZ targets a broad range of CpG-rich promoters through physical association with RNA Pol II and MLL. Leukemic MOZ-TIF2 fusion constitutively activates CpG-rich promoters by aberrantly recruiting p300/CBP; pharmacological inhibition of MLL or DOT1L induces differentiation of MOZ-TIF2-transformed cells. ChIP-seq, co-immunoprecipitation (MOZ-RNAP2/MLL), pharmacological inhibition, differentiation assay Cell reports Medium 32997997
2021 KAT6A acetylates SMAD3 at K20 and K117; this promotes SMAD3 association with TRIM24 and disrupts SMAD3 interaction with TRIM33. Acetylated H3K23 (by KAT6A) then recruits the TRIM24-SMAD3 complex to chromatin, increasing SMAD3 activation and cytokine expression, leading to MDSC recruitment and TNBC metastasis. Mass spectrometry, co-immunoprecipitation, ChIP, acetyltransferase assay, in vivo xenograft metastasis model Advanced science High 34392614
2021 KAT6A acetylates COP1 (an E3 ubiquitin ligase) at K294; COP1 acetylation impairs its E3 ubiquitin ligase function, leading to accumulation and enhanced activity of β-catenin, promoting ovarian cancer progression. Mass spectrometry, co-immunoprecipitation, in vivo ubiquitination assay, in vitro acetyltransferase assay, in vivo xenograft model Theranostics High 33995658
2022 KAT6A initiates a transcriptional control module in AML in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyl-lysine reader ENL, which cooperates with chromatin factors to induce transcriptional elongation. KAT6A was identified as a regulator of myeloid differentiation in a CRISPR screen, and its inhibition has anti-AML effects in vitro and in vivo. CRISPR screen, ChIP-seq (H3K9ac, ENL), co-immunoprecipitation, in vitro and in vivo AML models Cancer discovery High 34853079
2022 MOZ and Menin-MLL chromatin complexes are cooperative dependencies in GIST; MOZ inhibition disrupts interactions with transcriptional/chromatin regulators including DOT1L and reduces GIST cell proliferation in vivo. Genome-scale CRISPR screen, ChIP-seq, pharmacological inhibition, in vivo tumor model Cancer discovery High 35499757
2022 Endogenous MOZ is required for AML development induced by MLL-AF9, MLL-AF10, and MOZ-TIF2; MOZ maintains active histone modifications at the Meis1 (and Hoxa9) loci. Meis1 re-expression rescues MOZ-TIF2-induced AML in Moz-deficient cells; Meis1 deletion impairs MOZ-TIF2-mediated AML development. Conditional Moz-knockout HSPCs, retroviral transduction, in vivo AML model, ChIP for active histone marks, Meis1 rescue/deletion Blood advances High 35947126
2023 A winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs, and this DNA-binding function is responsible for genome-wide association of KAT6A with unmethylated CpG islands. Mutation of key WH1 DNA-binding residues completely abrogates KAT6A enrichment at CGIs and acts as dominant negative for H3K9 acetylation, comparable to HAT domain mutation. ChIP-seq, mutagenesis of WH domain, dominant-negative overexpression, H3K9ac ChIP, structural characterization Nucleic acids research High 36537216
2023 Two winged helix (WH) domains (WH1 and WH2) in MORF and MOZ bind DNA cooperatively, with WH1 specifically recognizing unmethylated CpG sequences. Cryo-EM, NMR, MS and mutagenesis show WH1 associates with CpG-containing linker DNA and WH2 binds the nucleosome dyad; WHs target MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation. WH1 also recruits oncogenic fusions to HOXA genes. Cryo-EM, NMR, mass spectrometry, mutagenesis, ChIP-seq, transcriptional assay Nature communications High 36754959
2024 KAT6A (MOZ/MORF) enzymatic (acyltransferase) activity and the MOZ-TIF2 protein itself are necessary for indefinite proliferation in a MOZ-TIF2 leukemia cell model. MOZ-TIF2 directly regulates a small subset of developmental transcription factor genes and correlates with enrichment of histone H3K23 propionylation (a newly described acylation mark) at these genes. Pharmacological inhibition, targeted protein degradation (dTAG), ChIP-seq (H3K23pr), gene expression profiling Proceedings of the National Academy of Sciences of the United States of America High 38889153
2024 KAT6A deficiency impairs synaptic structure and plasticity in hippocampal CA3 and causes memory deficits in mice. KAT6A transcriptionally regulates Rspo2 (encoding Wnt activator R-spondin 2) in CA3; restoring RSPO2 expression in CA3 neurons rescues Wnt signaling deficits and learning-associated behaviors in Kat6a mutant mice. Conditional KAT6A KO mice, viral RSPO2 rescue, electrophysiology, behavioral assays, Wnt pathway readouts Science advances High 38758792
2024 KAT6A undergoes liquid-liquid phase separation (LLPS) facilitated by APEX1, forming a stable KAT6A-PARP1-APEX1 complex that reduces PARP1 trapping at DNA break sites and confers PARP inhibitor resistance in ovarian cancer; inhibition of KAT6A LLPS (but not its catalytic activity) restores PARPi sensitivity. LLPS assays, co-immunoprecipitation, in vitro PARPi trapping assays, in vivo xenograft model Advanced science Medium 38973255
2025 KAT6A and KAT7, together with their shared subunit BRPF1, associate with NUP98 fusion oncoproteins on chromatin and within condensates in NUP98-rearranged AML. KAT6A inhibition decreases global H3K23ac, displaces NUP98::HOXA9 from the Meis1 locus, and leads to myeloid differentiation; combined KAT6A/7 and menin inhibition is synergistic. Co-immunoprecipitation, ChIP-seq (H3K23ac), genome-scale CRISPR screen, pharmacological inhibition, xenograft mouse model Cancer discovery High 40536430

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer cell 532 15607963
1997 mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila. The EMBO journal 393 9155031
2018 Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth. Nature 236 30069049
1998 A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Blood 220 9558366
2001 Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. The EMBO journal 199 11742995
2008 Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes. Molecular and cellular biology 192 18794358
2006 MOZ is essential for maintenance of hematopoietic stem cells. Genes & development 171 16702405
2003 MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer cell 171 12676584
2000 MOZ is fused to p300 in an acute monocytic leukemia with t(8;22). Genes, chromosomes & cancer 137 10824998
2002 MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene 135 11965546
2013 MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proceedings of the National Academy of Sciences of the United States of America 130 23431171
2001 Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation. Leukemia 128 11243405
2007 MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells. Oncogene 119 17694082
2015 De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay. American journal of human genetics 117 25728775
1998 Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2. Blood 116 9731070
2004 moz regulates Hox expression and pharyngeal segmental identity in zebrafish. Development (Cambridge, England) 113 15128673
2015 MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease. Biochimica et biophysica acta 107 25920810
2012 Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription. Genes & development 104 22713874
2001 The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Oncogene 104 11313971
2017 Histone Acetyltransferase KAT6A Upregulates PI3K/AKT Signaling through TRIM24 Binding. Cancer research 102 29021135
2021 KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 87 34392614
2016 MOZ (KAT6A) is essential for the maintenance of classically defined adult hematopoietic stem cells. Blood 87 27663673
2012 MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Developmental cell 83 22921202
2022 KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs. Cancer discovery 82 34853079
2010 PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nature medicine 81 20418886
2006 Moz-dependent Hox expression controls segment-specific fate maps of skeletal precursors in the face. Development (Cambridge, England) 81 16774997
1997 Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement. Blood 78 9376594
2020 The key roles of the lysine acetyltransferases KAT6A and KAT6B in physiology and pathology. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 77 33130515
2012 Tandem PHD fingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin. Journal of molecular biology 77 23063713
2015 MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway. Oncogene 75 25772242
2019 NEAT1-TFE3 and KAT6A-TFE3 renal cell carcinomas, new members of MiT family translocation renal cell carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 72 30622287
2008 Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest. The Journal of biological chemistry 69 19001415
2004 Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Genes, chromosomes & cancer 66 15101047
2014 MOZ-mediated repression of p16(INK) (4) (a) is critical for the self-renewal of neural and hematopoietic stem cells. Stem cells (Dayton, Ohio) 65 24307508
2008 MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish. British journal of haematology 65 18729850
2016 Identification of MYST3 as a novel epigenetic activator of ERα frequently amplified in breast cancer. Oncogene 57 27893709
2011 Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related factor (MORF). The Journal of biological chemistry 57 21880731
2021 KAT6A, a novel regulator of β-catenin, promotes tumorigenicity and chemoresistance in ovarian cancer by acetylating COP1. Theranostics 54 33995658
2014 KAT6A, a chromatin modifier from the 8p11-p12 amplicon is a candidate oncogene in luminal breast cancer. Neoplasia (New York, N.Y.) 52 25220592
2023 Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer. Cell chemical biology 51 37557181
2014 Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ. Proceedings of the National Academy of Sciences of the United States of America 51 24979783
2003 Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ. Nucleic acids research 51 12771199
2016 Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder. American journal of medical genetics. Part A 48 27133397
2009 Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons. Developmental biology 47 19254709
2015 MOZ regulates B-cell progenitors and, consequently, Moz haploinsufficiency dramatically retards MYC-induced lymphoma development. Blood 46 25605372
2012 Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene. Leukemia 46 23022987
2005 MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function. Molecular and cellular biology 46 15657427
2013 The MYSTerious MOZ, a histone acetyltransferase with a key role in haematopoiesis. Immunology 43 23347099
2006 MOZ fusion proteins in acute myeloid leukaemia. Biochemical Society symposium 43 16626284
2010 Chromosome 8p11.2 translocations: prevalence, FISH analysis for FGFR1 and MYST3, and clinicopathologic correlates in a consecutive cohort of 13 cases from a single institution. American journal of hematology 40 20143402
2004 RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications. Leukemia 40 15085163
2014 The MOZ histone acetyltransferase in epigenetic signaling and disease. Journal of cellular physiology 39 24633655
2008 Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases. Leukemia 39 18818702
2000 RT-PCR analysis of the MOZ-CBP and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13). Genes, chromosomes & cancer 35 10862050
2013 Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion. International journal of hematology 33 24258712
2003 Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11). Genes, chromosomes & cancer 32 12619166
2015 MOZ and BMI1 play opposing roles during Hox gene activation in ES cells and in body segment identity specification in vivo. Proceedings of the National Academy of Sciences of the United States of America 31 25922517
2020 Activation of CpG-Rich Promoters Mediated by MLL Drives MOZ-Rearranged Leukemia. Cell reports 30 32997997
2020 Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum. Orphanet journal of rare diseases 29 32041641
2023 The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA binding winged helix domain. Nucleic acids research 28 36537216
2022 MOZ and Menin-MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor. Cancer discovery 27 35499757
2022 BRPF1-KAT6A/KAT6B Complex: Molecular Structure, Biological Function and Human Disease. Cancers 27 36077605
2021 KAT6A regulates stemness of aging bone marrow-derived mesenchymal stem cells through Nrf2/ARE signaling pathway. Stem cell research & therapy 27 33541408
2019 Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter. The Journal of biological chemistry 26 31273084
2018 Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells. Blood 26 29371181
2017 Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target developmental genes in Drosophila. Genes & development 26 29070704
1999 A case of inv(8)(p11q24) associated with acute myeloid leukemia involves the MOZ and CBP genes in a masked t(8;16). Genes, chromosomes & cancer 26 10469454
2016 Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity. Cell reports 25 27653692
2018 MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development. iScience 24 30616103
2015 Mesodermal expression of Moz is necessary for cardiac septum development. Developmental biology 24 25912687
2014 The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t(8;19)(p11;q13). Genes, chromosomes & cancer 24 24446090
2007 MOZ and MOZ-CBP cooperate with NF-kappaB to activate transcription from NF-kappaB-dependent promoters. Experimental hematology 24 17920756
2006 MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta2 promoter: differential effects of MOZ fusion proteins on CBP- and MOZ-dependent activators. The Journal of biological chemistry 23 16613851
2023 MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain. Nature communications 22 36754959
2022 Matrix stiffness-induced upregulation of histone acetyltransferase KAT6A promotes hepatocellular carcinoma progression through regulating SOX2 expression. British journal of cancer 22 35332266
2021 The role of MOZ/KAT6A in hematological malignancies and advances in MOZ/KAT6A inhibitors. Pharmacological research 22 34626770
2003 Genomic characterization of MOZ/CBP and CBP/MOZ chimeras in acute myeloid leukemia suggests the involvement of a damage-repair mechanism in the origin of the t(8;16)(p11;p13). Genes, chromosomes & cancer 21 12461753
2023 The MOZ-BRPF1 acetyltransferase complex in epigenetic crosstalk linked to gene regulation, development, and human diseases. Frontiers in cell and developmental biology 19 36712963
2016 The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells. Experimental cell research 19 27256846
2003 A further case of acute myelomonocytic leukemia with inv(8) chromosomal rearrangement and MOZ-NCOA2 gene fusion. International journal of molecular medicine 19 12964013
2021 KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP. Biochemical and biophysical research communications 18 34808502
2018 A KAT6A variant in a family with autosomal dominantly inherited microcephaly and developmental delay. Journal of human genetics 18 29899504
2014 Comparison between karyotyping-FISH-reverse transcription PCR and RNA-sequencing-fusion gene identification programs in the detection of KAT6A-CREBBP in acute myeloid leukemia. PloS one 17 24798186
2003 Expression, purification, and analysis of MOZ and MORF histone acetyltransferases. Methods (San Diego, Calif.) 16 12893170
2016 MOZ and BMI1 act synergistically to maintain hematopoietic stem cells. Experimental hematology 15 27773671
2020 Concentration Dependence of the Unbound Partition Coefficient Kpuu and Its Application to Correct for Exposure-Related Discrepancies between Biochemical and Cellular Potency of KAT6A Inhibitors. Drug metabolism and disposition: the biological fate of chemicals 14 32357973
2024 KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13 38973255
2022 miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression. Anti-cancer drugs 13 34459452
2025 KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia. Cancer discovery 12 40536430
2024 Cold atmospheric plasma restores skewed macrophage polarization in triple negative breast cancers via enhancing KAT6A acetylation. Free radical biology & medicine 12 39586381
2023 In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A. Molecules (Basel, Switzerland) 12 36770785
2016 Expression of the MOZ-TIF2 oncoprotein in mice represses senescence. Experimental hematology 12 26854485
2007 New types of MYST3-CBP and CBP-MYST3 fusion transcripts in t(8;16)(p11;p13) acute myeloid leukemias. Haematologica 12 17296583
2024 KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3. Science advances 11 38758792
2024 A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes. Proceedings of the National Academy of Sciences of the United States of America 11 38889153
2021 Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review. BMC medical genomics 11 34930245
2017 Three brothers with a nonsense mutation in KAT6A caused by parental germline mosaicism. Human genome variation 11 31754438
2025 Targeting KAT6A/B as a New Therapeutic Strategy for Cancer Therapy. Journal of medicinal chemistry 10 39761381
2022 MOZ is critical for the development of MOZ/MLL fusion-induced leukemia through regulation of Hoxa9/Meis1 expression. Blood advances 10 35947126
2018 Paroxysmal Movement Disorder and Epilepsy Caused by a De Novo Truncating Mutation in KAT6A. Journal of pediatric genetics 10 30105118