Affinage

Showing KAT8 — MOF is a alias.

KAT8

Histone acetyltransferase KAT8 · UniProt Q9H7Z6

Length
458 aa
Mass
52.4 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KAT8 (hMOF/MYST1) is a MYST-family lysine acetyltransferase that controls chromatin state and gene expression principally through histone H4 acetylation, and additionally acts on a broad set of non-histone substrates to regulate genome stability, redox balance, immunity, and mitochondrial function (PMID:16024812, PMID:33657400). It catalyzes the bulk of cellular H4K16 acetylation as part of the MSL complex (with partners including hMSL3), while in the NSL complex it deposits H4K5ac and H4K8ac to drive transcription initiation at housekeeping gene promoters; depletion experiments show the NSL function is essential for cell survival whereas MSL/H4K16ac is dispensable for proliferation and chromatin accessibility (PMID:16024812, PMID:33657400). Its catalytic mechanism is ping-pong, with acetyl-CoA binding first followed by substrate, and depends on autoacetylation of the MYST domain at K274, which stabilizes the enzyme and is required for activity—any substitution at K274 disorders the active-site loop and abolishes function (PMID:26505788, PMID:27382063, PMID:21502975). KAT8 is genetically essential in vivo: its loss blocks embryonic development past the blastocyst stage with specific failure of H4K16ac and induction of apoptosis (PMID:18541669), and tissue-specific deletion impairs oocyte and trophoblast development, the latter via H4K16ac-dependent control of CDX2 (PMID:28506985, PMID:38961108). Through H4K16ac it couples chromatin to the DNA-damage response, interacting with ATM and supporting ATM activation and repair after ionizing radiation (PMID:15923642, PMID:16024812), and regulates RNA Pol II pause release via BRD4/pTEFb recruitment (PMID:21321083). KAT8 also extends acetylation to non-histone targets to tune diverse pathways: it acetylates IRF3 to suppress type-I interferon responses (PMID:30842237), Nrf2 to promote its nuclear retention and antioxidant gene expression (PMID:24571482), LSD1 to restrain EMT (PMID:27292636), and DBC1 to modulate SirT1 activity (PMID:24126058). A distinct mitochondrial pool, dependent on the NSL component KANSL3, binds mtDNA and is required for oxidative phosphorylation and respiratory gene transcription, with catalytic activity necessary for rescue (PMID:27768893); in mitochondria KAT8 acetylates the complex IV assembly factor COX17 and ATP5B to govern respiration and energy metabolism (PMID:37813994, PMID:39392752). KAT8 itself is regulated by SIRT1-mediated deacetylation of its MYST domain, which inhibits activity and promotes ubiquitin-dependent degradation, and by USP10-mediated deubiquitination that stabilizes the protein (PMID:21502975, PMID:22586264, PMID:38317006). Beyond classical acetylation, KAT8 also functions as a lactyltransferase and butyrylation writer for substrates including eEF1A2 and HSP90 (PMID:38359291, PMID:37460462). KAT8 contributes to malignancy, supporting MLL-AF9-driven leukemogenesis in a catalytic-activity-dependent manner (PMID:28202522).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2005 High

    Established KAT8 as the enzyme responsible for the bulk of mammalian H4K16 acetylation and linked it physically and functionally to the DNA-damage response.

    Evidence siRNA knockdown with mass spectrometry of endogenous histones, Co-IP with hMSL3 and ATM, kinase and DNA repair assays in human cells

    PMID:15923642 PMID:16024812

    Open questions at the time
    • Did not resolve which complex (MSL vs NSL) drives the repair phenotype
    • Mechanism of ATM activation by H4K16ac left structural
  2. 2008 High

    Demonstrated that KAT8 is non-redundantly required for development and that its function is specific to H4K16, not other histone lysines.

    Evidence Mof-null/conditional knockout mouse embryos with immunofluorescence, Western blot, and caspase-3 assays; gene-specific TMS1 ChIP studies

    PMID:18541669 PMID:18701507

    Open questions at the time
    • Did not separate chromatin vs non-histone roles in lethality
    • Downstream gene programs underlying apoptosis not fully mapped
  3. 2011 High

    Defined autoacetylation at K274 in the MYST domain as a regulatory switch and SIRT1 as its eraser controlling chromatin recruitment.

    Evidence In vitro acetylation and nucleosome-binding assays, Co-IP, and ChIP

    PMID:21321083 PMID:21502975

    Open questions at the time
    • Whether autoacetylation is intramolecular or intermolecular not settled
    • Quantitative contribution of autoacetylation vs SIRT1 in vivo unclear
  4. 2012 High

    Showed SIRT1 deacetylation of the MYST domain inhibits KAT8 activity and triggers its degradation, coupling enzyme turnover to DNA damage.

    Evidence In vitro deacetylation, mutagenesis of target lysines, ubiquitination and DSB repair assays

    PMID:22586264

    Open questions at the time
    • E3 ligase mediating degradation not identified
    • Kinetics of transient SIRT1 dissociation after damage not quantified
  5. 2013 High

    Connected KAT8/H4K16ac to autophagy outcome and to non-histone control of SirT1 activity via DBC1 acetylation.

    Evidence Genome-wide ChIP-seq, siRNA knockdown, viability assays; in vitro DBC1 acetylation with mutagenesis

    PMID:23863932 PMID:24126058

    Open questions at the time
    • Signal triggering KAT8 downregulation during autophagy not fully defined
    • Interplay between chromatin and DBC1 routes not integrated
  6. 2015 High

    Resolved the enzymatic mechanism as ordered ping-pong with acetyl-CoA binding first, providing a kinetic framework and inhibitor basis.

    Evidence Enzyme kinetics and isothermal titration calorimetry with anacardic acid inhibitor analysis

    PMID:26505788

    Open questions at the time
    • Done with isolated enzyme, not in complex context
    • Substrate selectivity within MSL vs NSL not addressed kinetically
  7. 2016 High

    Established a catalytically required mitochondrial pool of KAT8 controlling oxidative phosphorylation and mtDNA transcription, and structurally explained K274 dependence.

    Evidence Subcellular fractionation, ChIP on mtDNA, cardiac conditional knockout, catalytic-mutant rescue; X-ray crystallography of K274P mutant

    PMID:24571482 PMID:27292636 PMID:27382063 PMID:27768893

    Open questions at the time
    • Mechanism of KAT8 mitochondrial import not defined
    • Mitochondrial substrates incompletely catalogued at this stage
  8. 2019 High

    Extended KAT8 function to innate immunity by showing direct IRF3 acetylation suppresses type-I interferon responses.

    Evidence Co-IP, in vitro acetylation, ChIP, and mouse viral challenge

    PMID:30842237

    Open questions at the time
    • Whether nuclear vs cytoplasmic KAT8 acts on IRF3 unclear
    • Complex dependence of IRF3 acetylation not defined
  9. 2021 High

    Separated KAT8 functions by complex: NSL-driven H4K5/K8ac is essential for housekeeping transcription whereas MSL-driven H4K16ac is dispensable for proliferation.

    Evidence Auxin-inducible degron depletion with mass spectrometry, ATAC-seq, RNA-seq, ChIP-seq; fibrosis ChIP/rescue work

    PMID:33657400 PMID:34285225

    Open questions at the time
    • How complex partitioning is regulated in cells not resolved
    • Reconciliation with earlier H4K16ac-essential phenotypes incomplete
  10. 2023 High

    Broadened the substrate and modification repertoire to mitochondrial COX17 acetylation and to condensate-based IRF1 acetylation controlling PD-L1, plus butyrylation of HSP90.

    Evidence In vitro acetylation, Co-IP, electron microscopy and acetyl-mimetic rescue; phase-separation assays with blocking peptide and tumor models; butyrylome profiling

    PMID:36894639 PMID:37460462 PMID:37813994 PMID:39207899

    Open questions at the time
    • Determinants of substrate vs modification choice (acetyl/butyryl) unknown
    • Physiological triggers for condensate formation incompletely defined
  11. 2024 High

    Identified KAT8 as a lactyltransferase writer acting on eEF1A2, PCK2, and other targets, and confirmed USP10-mediated stabilization controlling its oncogenic output.

    Evidence Lactylome profiling, in vitro lactylation, Co-IP, ubiquitination assays, and KAT8 deletion/gene-edited mouse models

    PMID:38317006 PMID:38359291 PMID:39392752 PMID:39853940

    Open questions at the time
    • Active-site basis for lactyl vs acetyl transfer not structurally defined
    • How metabolic lactate levels gate KAT8 writer activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single MYST enzyme selects among acyl-CoA donors (acetyl, lactyl, butyryl), histone vs non-histone substrates, and nuclear vs mitochondrial compartments remains the central open question.
  • No structural model distinguishing donor selectivity
  • Regulation of compartmental partitioning between nucleus and mitochondria undefined
  • Rules governing complex assembly (MSL vs NSL) in different cell types unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 5 GO:0003677 DNA binding 3 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005739 mitochondrion 3
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 3 R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2
Partners
ATMIRF3KANSL3LSD1MSL3NRF2SIRT1USP10
Complex memberships
MSL complexNSL complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 hMOF (KAT8) is a histone H4 lysine 16-specific acetyltransferase required for bulk H4K16 acetylation in mammalian cells. Knockdown of hMOF in HeLa and HepG2 cells causes dramatic reduction of H4K16ac (confirmed by Western blot and mass spectrometry). hMOF and hMSL3 form a complex in mammalian cells. hMOF-depleted cells accumulate in G2/M and show impaired DNA damage repair response to ionizing radiation, with increased phospho-ATM and γH2AX foci. siRNA knockdown, Western blot, mass spectrometric analysis of endogenous histones, co-immunoprecipitation Molecular and cellular biology High 16024812
2005 hMOF interacts with ATM protein, and hMOF-dependent H4K16ac is required for ATM autophosphorylation, ATM kinase activity, and downstream effector phosphorylation after ionizing radiation. Blocking H4K16ac increase (via dominant-negative hMOF or siRNA) decreases ATM function and DNA repair while increasing cell killing. Co-immunoprecipitation, dominant-negative mutant expression, siRNA knockdown, kinase assays, immunofluorescence Molecular and cellular biology High 15923642
2008 Mof (KAT8) is essential for embryonic development past the blastocyst stage in mice. Mof-null embryos fail to acetylate H4K16 but have normal acetylation of other histone lysine residues, demonstrating non-redundant and specific function. Loss of Mof causes abnormal chromatin aggregation preceding caspase-3 activation and DNA fragmentation. Conditional knockout mouse model, immunofluorescence, Western blot, caspase-3 assay Molecular and cellular biology High 18541669
2013 Autophagy induction leads to downregulation of hMOF, causing reduction of H4K16ac, which is associated predominantly with downregulation of autophagy-related genes. Antagonizing H4K16ac downregulation during autophagy induction promotes cell death, establishing a feedback loop where H4K16ac levels determine the survival vs. death outcome of autophagy. Western blot, genome-wide ChIP-seq, siRNA knockdown, cell viability assays Nature High 23863932
2016 KAT8/MOF and a subset of its NSL complex partners reside in mitochondria in addition to the nucleus. Mitochondrial MOF binds mtDNA (dependent on KANSL3) and regulates oxidative phosphorylation by controlling expression of respiratory genes from both nuclear and mtDNA. A catalytically deficient MOF mutant fails to rescue respiratory and mtDNA transcriptional defects, indicating catalytic activity is required. Subcellular fractionation, ChIP, conditional knockout mouse model (cardiac), RNA-seq, catalytic mutant rescue experiments Cell High 27768893
2021 KAT8 exhibits complex-dependent catalytic activity: as part of the NSL complex it catalyzes H4K5ac and H4K8ac, whereas as part of the MSL complex it catalyzes the bulk of H4K16ac. MSL complex proteins and H4K16ac are not required for cell proliferation and chromatin accessibility, whereas the NSL complex is essential for cell survival by stimulating transcription initiation at housekeeping gene promoters. Auxin-inducible degron system for protein depletion, mass spectrometry, ATAC-seq, RNA-seq, ChIP-seq Molecular cell High 33657400
2012 SIRT1 deacetylates the enzymatic (MYST) domains of hMOF and TIP60, inhibiting their acetyltransferase activity and promoting ubiquitination-dependent degradation. Immediately following DNA damage, SIRT1 binding to hMOF is transiently interrupted with corresponding hMOF hyperacetylation. Lysine-to-arginine mutations at SIRT1-targeted lysines on hMOF repress DNA double-strand break repair and inhibit apoptosis induction. Co-immunoprecipitation, in vitro deacetylation assay, mutagenesis, ubiquitination assay, DNA damage repair assays Molecular and cellular biology High 22586264
2011 hMOF undergoes autoacetylation in vitro and in vivo, restricted to the MYST domain with K274 as the major autoacetylation site. SIRT1 interacts with the MYST domain of hMOF and deacetylates it. Non-acetylated hMOF binds nucleosomes more robustly; acetylation decreases nucleosome binding. SIRT1 deacetylation of hMOF promotes its chromatin recruitment and H4K16ac activity. In vitro acetylation assay, co-immunoprecipitation, in vitro nucleosome binding assay, ChIP, siRNA knockdown Cell research High 21502975
2016 Structural and mutational analysis of hMOF K274 autoacetylation reveals that all amino acid substitutions at K274 result in significant destabilization of hMOF and complete loss of catalytic activity toward histone H4. X-ray crystal structure of K274P mutant shows disordering of the α2-β7 loop harboring K274, explaining loss of function. K274 autoacetylation (driven by Ac-CoA binding) is required for hMOF stability and cognate substrate acetylation. X-ray crystallography, mutagenesis, in vitro acetyltransferase assay, stability measurements The Journal of biological chemistry High 27382063
2015 KAT8 follows a ping-pong kinetic mechanism in which Ac-CoA binds first, followed by the histone substrate. This was confirmed by isothermal titration calorimetry (ITC) affinity measurements of both substrates. Anacardic acid inhibits KAT8 via this mechanism and the inhibition constants of anacardic acid derivatives were calculated. Enzyme kinetics, isothermal titration calorimetry (ITC), inhibitor assays European journal of medicinal chemistry High 26505788
2019 KAT8 directly interacts with IRF3 via its MYST domain and mediates IRF3 acetylation at lysine 359, inhibiting IRF3 recruitment to IFN-I gene promoters and decreasing its transcriptional activity. KAT8 deficiency in mice protects from viral challenge by enhancing IFN-I production. Co-immunoprecipitation, in vitro acetylation assay, ChIP, siRNA screen, mouse viral challenge model The Journal of experimental medicine High 30842237
2023 In response to IFNγ, KAT8 undergoes phase separation with IRF1 and forms biomolecular condensates, which promotes IRF1 K78 acetylation and its binding to the PD-L1 (CD274) promoter, enriching transcription apparatus and upregulating PD-L1 mRNA. Multivalency from specific and promiscuous IRF1-KAT8 interactions is required for condensate formation. A blocking peptide (2142-R8) that disrupts KAT8-IRF1 condensate formation inhibits PD-L1 expression and enhances antitumor immunity. Phase separation assays, Co-immunoprecipitation, in vitro acetylation assay, ChIP, blocking peptide experiments, in vivo tumor models Nature cancer High 36894639
2014 hMOF physically interacts with Nrf2 and acetylates it at Lys588. MOF-mediated acetylation increases nuclear retention of Nrf2 and transcription of its downstream genes. MOF/hMOF is essential for anti-oxidative and anti-drug responses in an Nrf2-dependent manner. Co-immunoprecipitation, in vitro acetylation assay, nuclear fractionation, siRNA knockdown, reporter assay, mouse xenograft British journal of pharmacology High 24571482
2013 hMOF (KAT8) is responsible for acetylation of DBC1/CCAR2 at K112 and K215. Acetylation of these residues inhibits DBC1-SirT1 binding and increases SirT1 deacetylase activity. After DNA damage, ATM-dependent inhibition of hMOF binding to DBC1 leads to DBC1 deacetylation and increased SirT1-DBC1 binding. A DBC1 acetylation-mimic mutant fails to promote apoptosis after DNA damage. Co-immunoprecipitation, in vitro acetylation assay, mutagenesis, DNA damage assays Molecular and cellular biology High 24126058
2016 MOF acetyltransferase interacts with LSD1 and is responsible for acetylation of LSD1 in epithelial cells. Acetylation of LSD1 reduces its association with nucleosomes, increasing H3K4 methylation at LSD1 target genes and activating transcription. MOF expression is downregulated by EMT-inducing signals, and MOF depletion enhances EMT and tumor metastasis. Co-immunoprecipitation, in vitro acetylation assay, nucleosome association assay, ChIP, siRNA knockdown Cell reports High 27292636
2011 SUV420H2-mediated H4K20me3 and hMOF-mediated H4K16ac play opposing roles in RNA Pol II promoter-proximal pausing. H4K16ac promotes release of Pol II from pausing through recruitment of BRD4 and pTEFb. H4K20me3 blocks Pol II escape by locally inhibiting H4K16ac. Combined inhibition of H4K20me3 and DNA methylation results in re-recruitment of hMOF, H4K16ac, and synergistic reactivation of gene expression. ChIP, siRNA knockdown, inhibitor treatments, reporter assays Molecular and cellular biology High 21321083
2014 MOF (MSL complex) specifically regulates Tsix, the major repressor of Xist lncRNA, in mouse embryonic stem cells. MSL depletion leads to decreased Tsix expression, reduced REX1 recruitment, and consequently enhanced Xist accumulation and variable X-chromosome inactivation during differentiation. The NSL complex provides additional Tsix-independent repression of Xist by maintaining pluripotency. ChIP-seq, RNA-seq, siRNA knockdown, allele-specific analysis eLife High 24842875
2021 TGFβ activates autophagy via SMAD3-dependent downregulation of MYST1 (KAT8), which regulates expression of core autophagy components ATG7 and BECLIN1 via H4K16 acetylation. Autophagy activation in fibroblasts promotes collagen release and is required to induce tissue fibrosis. Forced expression of MYST1 abrogates TGFβ-stimulated autophagy. ChIP, siRNA knockdown, overexpression, mouse fibrosis models, Western blot Nature communications High 34285225
2023 MOF (via its KANSL complex) acetylates COX17, a complex IV assembly factor, at a specific residue. Loss of MOF-KANSL complex leads to mitochondrial fragmentation, reduced cristae density, and impaired electron transport chain complex IV integrity. Expression of acetylation-mimetic COX17 rescues these defects even in the absence of MOF, demonstrating that COX17 acetylation is a critical downstream effector of MOF in mitochondrial physiology. Co-immunoprecipitation, in vitro acetylation assay, mitochondrial fractionation, electron microscopy, acetylation-mimetic mutant rescue experiments, patient fibroblasts Nature metabolism High 37813994
2024 KAT8 acts as a pan-lactyltransferase (Kla writer) capable of installing lysine lactylation on multiple protein substrates. KAT8 specifically lactylates eEF1A2 at K408, boosting translation elongation and protein synthesis contributing to colorectal cancer tumorigenesis. Deletion of KAT8 inhibited CRC tumor growth, especially in high-lactic tumor microenvironments. Proteomics/lactylome profiling, co-immunoprecipitation, in vitro lactylation assay, KAT8 deletion mouse models Proceedings of the National Academy of Sciences of the United States of America High 38359291
2017 MOF HAT activity is required for MLL-AF9-driven leukemogenesis. Conditional deletion of Mof in MLL-AF9 mouse leukemia model reduced tumor burden and prolonged survival. Rescue experiments with catalytically inactive MOF mutants showed enzymatic activity is required for cancer pathogenicity. MOF loss impaired global H4K16ac and increased γH2AX foci. Conditional knockout mouse model, catalytic mutant rescue experiments, RNA-seq, immunofluorescence Cancer research High 28202522
2017 KAT8 is essential for mouse oocyte development. Oocyte-specific deletion of Kat8 causes female infertility with follicle development failure. KAT8 deficiency results in significant downregulation of antioxidant genes with consequent ROS increase, which can be rescued by N-acetylcysteine. ChIP assays show KAT8 directly binds promoter regions of antioxidant genes. Conditional knockout (Gdf9-Cre), RNA-seq, ChIP, antioxidant rescue experiments (N-acetylcysteine injection) Development (Cambridge, England) High 28506985
2020 MOF regulates erythropoiesis by dynamic chromatin recruitment; its haploinsufficiency causes accumulation of a transient HSC population. A regulatory network of MOF, RUNX1, and GFI1B is critical for erythroid fate commitment. GFI1B acts as a Mof activator necessary and sufficient for cell-type-specific induction of Mof expression. Mof-depleted HSC plasticity can be rescued by downstream effector GATA1 or HDAC inhibitor-mediated rebalancing of acetylation. Single-cell RNA-seq, ChIP-seq, genetic rescue experiments, HDAC inhibitor treatment Science advances High 32671208
2014 MYST1 (KAT8) co-stimulates androgen receptor (AR) and NF-κB functions in prostate cancer cells. NF-κB activation promotes SIRT1-mediated deacetylation of MYST1, and mutually exclusive interactions of MYST1 with SIRT1 vs. AR regulate H4K16ac. MYST1 depletion in AR-lacking cells triggers PARP/caspase-3 cleavage (apoptosis), while in AR-transformed cells it induces CDK N1A/p21 and G2M arrest. Co-immunoprecipitation, siRNA knockdown, ChIP, cell cycle analysis, Western blot Molecular endocrinology (Baltimore, Md.) Medium 24702180
2016 KAT8 colocalizes with WDR5 at androgen receptor (AR) target genes. PKN1/H3T11 phosphorylation leads to WDR5/MLL methyltransferase recruitment, which then recruits KAT8 to effect H4K16ac and AR-dependent gene activation. KAT8 knockdown significantly decreased AR target gene expression and prostate cancer cell proliferation. ChIP, siRNA knockdown, Co-immunoprecipitation, gene expression analysis Molecular endocrinology (Baltimore, Md.) Medium 27268279
2016 TET1 forms a chromatin complex with hMOF and Sin3a in mouse embryonic stem cells. TET1 facilitates chromatin affinity and enzymatic activity of hMOF toward H4K16ac by preventing hMOF autoacetylation, thereby regulating expression of downstream genes including DNA repair genes. Tet1 knockout cells show DNA damage accumulation and genomic instability. Co-immunoprecipitation, ChIP-seq analysis (integrative genomics), in vitro biochemical studies, Tet1 knockout MEF cells Nucleic acids research Medium 27733505
2018 MOF interacts with PCNA at replication forks and affects PCNA ubiquitination and recruitment to DNA damage sites. MOF depletion in cells under replicative stress decreases replication fork speed, increases stalled replication forks, promotes new origin firing, and increases R-loop formation. MOF depletion also compromises DNA end resection and CHK1 phosphorylation. Co-immunoprecipitation, DNA fiber assay, PCNA ubiquitination assay, immunofluorescence, siRNA knockdown Molecular and cellular biology Medium 29298824
2020 WSTF lysine 426 is acetylated by MOF (via MSL1v1-mediated interaction) and deacetylated by SIRT1. WSTF K426 acetylation promotes WSTF Ser158 phosphorylation, enhancing WSTF kinase and transcriptional regulatory activity and cancer cell proliferation, migration, and invasion. Co-immunoprecipitation, in vitro acetylation assay, mutagenesis, cell proliferation and invasion assays Oncogene Medium 32518374
2024 USP10 (a deubiquitinase) binds to and deubiquitinates MOF at lysine 410, protecting it from proteasome-dependent degradation. MOF stabilization by USP10 promotes H4K16ac enrichment at the ANXA2 promoter (in a JUN-dependent manner), stimulating ANXA2 transcription and activating Wnt/β-Catenin signaling to facilitate esophageal cancer progression. Catalytically inactive MOF-E350Q fails to promote progression. Co-immunoprecipitation, ubiquitination assay, ChIP, catalytic mutant rescue, siRNA knockdown, in vivo tumor models Oncogene High 38317006
2008 hMOF-mediated H4K16ac is specifically required for TMS1/ASC gene activity. Downregulation of hMOF or other MSL complex components causes gene-specific decrease in H4K16ac, loss of nucleosome positioning at TMS1, and silencing of TMS1 transcription. Gene silencing induced by H4K16 deacetylation occurs independently of changes in histone methylation and DNA methylation. ChIP, siRNA knockdown, bisulfite sequencing, gene expression analysis Cancer research Medium 18701507
2023 MOF acetylates PRDX1 (peroxiredoxin 1) at lysine 197, preventing its hyperoxidation and maintaining its peroxidase activity under stress. PRDX1 K197ac decreases in mouse macrophages stimulated with LPS but not IL-4 or IL-10. Loss of K197ac elevates cellular hydrogen peroxide and augments ERK1/2 phosphorylation, stimulating glycolysis, H3S28 phosphorylation, and pro-inflammatory mediator (IL-6) production. In vitro acetylation assay, mass spectrometry, macrophage stimulation assays, Western blot, siRNA knockdown Cell reports Medium 39207899
2024 KAT8-mediated H4K16ac regulates CDX2 transcription and is essential for trophoblast stem cell self-renewal and proliferation. Trophoblast-specific Kat8 deletion leads to extraembryonic ectoderm abnormalities and embryonic lethality. CDX2 overexpression partially rescues Kat8 knockout defects. Reduced KAT8, CDX2, and H4K16ac are associated with recurrent pregnancy loss in clinical samples, and EX527 (SIRT1 inhibitor) treatment restores CDX2 levels and placental development. Conditional knockout, RNA-seq, CUT&Tag, CDX2 rescue experiments, pharmacological rescue with EX527, trophoblast organoids Nature communications High 38961108
2024 KAT8 directly lactylates PCK2 (mitochondrial phosphoenolpyruvate carboxykinase 2) at Lys100, augmenting PCK2 kinase activity. PCK2-K100 lactylation competitively inhibits Parkin-mediated polyubiquitination of OXSM, leading to metabolic remodeling of mitochondrial fatty acid synthesis and exacerbating hepatic ferroptosis during ischemia/reperfusion injury. In vitro lactylation assay, gene-edited mice, Co-immunoprecipitation, ubiquitination assay Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39853940
2024 Mitochondria-localized MOF acetylates ATP5B at K201. Co-regulation of ATP5B K201 acetylation by MOF and SIRT3 impairs mitochondrial respiration and energy metabolism. Overexpression of mitochondria-targeted MOF in mice results in mitochondrial dysfunction, cardiac remodeling, and heart failure. SIRT3 knockout aggravates mtMOF-induced damage. Quantitative lysine acetylome analysis (mass spectrometry), conditional overexpression mouse model, SIRT3 knockout, in vitro respiration assays Cell reports High 39392752
2023 KAT8-mediated acetylation of YEATS4 at specific residues impairs YEATS4 interaction with HUWE1 (E3 ligase), preventing its ubiquitination and proteasomal degradation, thereby stabilizing YEATS4. KAT8 inhibitor MG149 decreases YEATS4 acetylation, reduces bladder cancer cell viability, and sensitizes cells to cisplatin. Co-immunoprecipitation, in vitro acetylation assay, ubiquitination assay, CRISPR-Cas9 screen, KAT8 inhibitor treatment Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 38526153
2023 KAT8 acetylates HSP90 at K754 as a lysine butyrylation (Kbu) writer, cooperating with HDAC11 as the eraser. SDCBP increases HSP90 K754 butyrylation and stability by competitively binding HDAC11. HSP90 Kbu contributes to 5-FU resistance in esophageal squamous cell carcinoma. Butyrylome profiling (mass spectrometry), co-immunoprecipitation, in vitro modification assay, gain/loss-of-function experiments Cell discovery Medium 37460462
2024 KAT8 triggers LTBP1 lactylation at lysine 752 (K752) via a KAT8-dependent mechanism in fibroblasts. Lactate (released from PLLA) is taken up via MCT1 and facilitates LTBP1 K752 lactylation, which increases collagen I and collagen III protein levels in fibroblasts. Lactylation assays, siRNA knockdown, Co-immunoprecipitation, Western blot International journal of biological macromolecules Low 39102921
2023 MOF (KAT8) directly binds promoter regions of Runx2 and Osterix and physically interacts with these osteogenic transcription factors, promoting their transcription via H4K16ac. MOF inhibition (siRNA or MG149 inhibitor) reduces Runx2/Osterix expression and inhibits osteoblast differentiation. ChIP, Co-immunoprecipitation, siRNA knockdown, small molecule inhibitor (MG149) Cell and tissue research Medium 37247031
2023 hMOF acetylates MDM2, increasing MDM2 stability by inhibiting its ubiquitinated degradation. Increased MDM2 acetylation by hMOF reduces cisplatin-induced p53 accumulation and promotes cisplatin resistance in ovarian cancer cells. Genetic inhibition of MDM2 reverses hMOF-mediated cisplatin resistance. Co-immunoprecipitation, ubiquitination assay, Western blot, RNA-seq, siRNA knockdown, xenograft mouse model Cell death discovery Medium 37291112
2017 Glioma-induced activation of microglia involves SIRT1 nuclear localization leading to deacetylation of hMOF, which in turn results in hMOF chromatin recruitment at promoter regions of microglial target genes and increased H4K16ac in microglia, promoting a tumor-supporting phenotype. Subcellular fractionation, ChIP, siRNA knockdown, cell co-culture model Oncoimmunology Medium 29308302
2017 Acetylation of hMOF modulates H4K16ac and DNA repair gene expression in response to oxidative stress. Hydrogen peroxide induces SIRT1, which decreases hMOF chromatin affinity and activity toward H4K16ac, resulting in decreased transcriptional expression of DNA repair genes independent of DNA methylation changes. RNA-seq, RRBS-seq, ChIP, siRNA knockdown International journal of biological sciences Medium 28808424
2013 KAT8 regulates G2/M cell cycle arrest through AKT/ERK-cyclin D1 signaling. KAT8 inhibition led to p53 induction and subsequently reduced Bcl-2 expression in lung cancer cells. RNAi screen, Western blot, flow cytometry, siRNA knockdown International journal of clinical and experimental pathology Low 23638218
2014 hMOF regulates the expression of SIRT6 and its downstream genes in hepatocellular carcinoma cells. hMOF knockdown promotes HCC growth while overexpression reduces it, and the effect is mechanistically linked to SIRT6 regulation. siRNA knockdown, overexpression, ChIP (implied), in vitro and in vivo tumor growth assays Biochemical and biophysical research communications Low 25181338
2015 MOF directly binds and maintains expression of cell cycle progression genes in proliferating cells (via NSL complex) but is dispensable for terminally differentiated podocytes under physiological conditions. Under injury stress, MOF is critical for podocyte maintenance, with genome-wide analysis revealing MOF directly binds lysosome, endocytosis, and vacuole pathway genes. Conditional knockout, ChIP-seq, RNA-seq, genome-wide expression analysis Oncogene Medium 26387537

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Enzyme-MOF (metal-organic framework) composites. Chemical Society reviews 686 28451673
2013 The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy. Nature 272 23863932
2005 hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Molecular and cellular biology 265 16024812
2024 KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 222 38359291
2005 Involvement of human MOF in ATM function. Molecular and cellular biology 186 15923642
2021 Designing MOF Nanoarchitectures for Electrochemical Water Splitting. Advanced materials (Deerfield Beach, Fla.) 181 33749910
2018 Enzyme-MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy. Angewandte Chemie (International ed. in English) 152 29536600
2016 MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria. Cell 150 27768893
2008 Mof (MYST1 or KAT8) is essential for progression of embryonic development past the blastocyst stage and required for normal chromatin architecture. Molecular and cellular biology 146 18541669
2020 Enzyme embedded metal organic framework (enzyme-MOF): De novo approaches for immobilization. International journal of biological macromolecules 129 31987954
2008 The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma. International journal of cancer 126 18058815
2007 Males absent on the first (MOF): from flies to humans. Oncogene 114 17694080
2023 Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity. Nature cancer 108 36894639
2023 MOF-derived bimetallic nanozyme to catalyze ROS scavenging for protection of myocardial injury. Theranostics 107 37215581
2023 MOF-On-MOF Dual Enzyme-Mimic Nanozyme with Enhanced Cascade Catalysis for Colorimetric/Chemiluminescent Dual-Mode Aptasensing. Analytical chemistry 107 37427434
2014 The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer. British journal of pharmacology 87 24571482
2021 TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy. Nature communications 82 34285225
2014 MOF-associated complexes ensure stem cell identity and Xist repression. eLife 82 24842875
2021 Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis. Molecular cell 80 33657400
2012 SIRT1 negatively regulates the activities, functions, and protein levels of hMOF and TIP60. Molecular and cellular biology 76 22586264
2011 SUV420H2-mediated H4K20 trimethylation enforces RNA polymerase II promoter-proximal pausing by blocking hMOF-dependent H4K16 acetylation. Molecular and cellular biology 76 21321083
2025 MOF-Based Electrocatalysts: An Overview from the Perspective of Structural Design. Chemical reviews 72 40070208
2016 MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition. Cell reports 72 27292636
2019 KAT8 selectively inhibits antiviral immunity by acetylating IRF3. The Journal of experimental medicine 71 30842237
2009 Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure. Toxicology and applied pharmacology 71 19732783
2023 Self-assembly of colloidal metal-organic framework (MOF) particles. Chemical Society reviews 70 36930224
2010 Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide. Oncogene 70 20118981
2008 Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity. Cancer research 70 18701507
2021 Natural Polymers Decorated MOF-MXene Nanocarriers for Co-delivery of Doxorubicin/pCRISPR. ACS applied bio materials 69 35007059
2023 Photodynamic Alginate Zn-MOF Thermosensitive Hydrogel for Accelerated Healing of Infected Wounds. ACS applied materials & interfaces 67 37129874
2016 The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis. International journal of molecular sciences 66 26784169
2020 Tip-To-Middle Anisotropic MOF-On-MOF Growth with a Structural Adjustment. Journal of the American Chemical Society 65 31968935
2024 MOFs and MOF-Based Composites as Next-Generation Materials for Wound Healing and Dressings. Small (Weinheim an der Bergstrasse, Germany) 59 38453672
2015 MOF maintains transcriptional programs regulating cellular stress response. Oncogene 58 26387537
2022 MOFs and MOF-Derived Materials for Antibacterial Application. Journal of functional biomaterials 57 36412856
2011 Modulations of hMOF autoacetylation by SIRT1 regulate hMOF recruitment and activities on the chromatin. Cell research 57 21502975
2020 Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development. Molecular and cellular biology 55 32661120
2023 Multi-Bioinspired MOF Delivery Systems from Microfluidics for Tumor Multimodal Therapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 50 37852943
2013 Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma. Journal of experimental & clinical cancer research : CR 50 23394073
2024 Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing. Journal of nanobiotechnology 48 38575979
2013 Histone acetyltransferase hMOF promotes S phase entry and tumorigenesis in lung cancer. Cellular signalling 47 23628702
2016 TET1 modulates H4K16 acetylation by controlling auto-acetylation of hMOF to affect gene regulation and DNA repair function. Nucleic acids research 46 27733505
2014 Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma. International journal of oncology 45 24452485
2023 Current status and prospects of MIL-based MOF materials for biomedicine applications. RSC medicinal chemistry 44 37859709
2023 Enhanced Bioactivity of Enzyme/MOF Biocomposite via Host Framework Engineering. Journal of the American Chemical Society 43 37671920
2017 Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis. Cancer research 43 28202522
2017 Histone acetyltransferase KAT8 is essential for mouse oocyte development by regulating reactive oxygen species levels. Development (Cambridge, England) 43 28506985
2025 The Lactate-Primed KAT8‒PCK2 Axis Exacerbates Hepatic Ferroptosis During Ischemia/Reperfusion Injury by Reprogramming OXSM-Dependent Mitochondrial Fatty Acid Synthesis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 41 39853940
2024 Ultrasound Trigger Ce-Based MOF Nanoenzyme For Efficient Thrombolytic Therapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 41 38576170
2024 MOF-Derived Nanoparticles with Enhanced Acoustical Performance for Efficient Mechano-Sonodynamic Therapy. Advanced materials (Deerfield Beach, Fla.) 40 38896775
2019 MOF-Based Nanotubes to Hollow Nanospheres through Protein-Induced Soft-Templating Pathways. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 40 30937262
2021 MOF@COF Heterostructure Hybrid for Dual-Mode Photoelectrochemical-Electrochemical HIV-1 DNA Sensing. Langmuir : the ACS journal of surfaces and colloids 37 34734735
2024 Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts. International journal of biological macromolecules 35 39102921
2014 The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth. Biochemical and biophysical research communications 34 25181338
2025 Mannosylated MOF Encapsulated in Lactobacillus Biofilm for Dual-Targeting Intervention Against Mammalian Escherichia coli Infections. Advanced materials (Deerfield Beach, Fla.) 32 40277329
2014 Coactivator MYST1 regulates nuclear factor-κB and androgen receptor functions during proliferation of prostate cancer cells. Molecular endocrinology (Baltimore, Md.) 32 24702180
2009 Is MOF an outcome parameter or a transient, adaptive state in critical illness? Current opinion in critical care 31 19617821
2020 The histone acetyltransferase hMOF promotes vascular invasion in hepatocellular carcinoma. Liver international : official journal of the International Association for the Study of the Liver 29 31943753
2020 Temporal expression of MOF acetyltransferase primes transcription factor networks for erythroid fate. Science advances 28 32671208
2020 Quasi-MOF derivative-based electrode for efficient electro-Fenton oxidation. Journal of hazardous materials 28 32763710
2015 Enzyme kinetics and inhibition of histone acetyltransferase KAT8. European journal of medicinal chemistry 28 26505788
2023 COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function. Nature metabolism 27 37813994
2018 MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks. Molecular and cellular biology 26 29298824
2016 KAT8 Regulates Androgen Signaling in Prostate Cancer Cells. Molecular endocrinology (Baltimore, Md.) 26 27268279
2020 Recent advances in fluorescence sensors based on DNA-MOF hybrids. Luminescence : the journal of biological and chemical luminescence 25 32064758
2015 Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma. International journal of oncology 25 25873202
2024 Stabilization of MOF (KAT8) by USP10 promotes esophageal squamous cell carcinoma proliferation and metastasis through epigenetic activation of ANXA2/Wnt signaling. Oncogene 24 38317006
2021 Role of histone acetyltransferases MOF and Tip60 in genome stability. DNA repair 24 34399315
2017 Glioma-induced SIRT1-dependent activation of hMOF histone H4 lysine 16 acetyltransferase in microglia promotes a tumor supporting phenotype. Oncoimmunology 24 29308302
2016 Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition. Cancer biology & therapy 23 27715462
2013 hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1. Molecular and cellular biology 23 24126058
2023 KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells. Cell death & disease 22 36849520
2023 Ligand-Screened Cerium-Based MOF Microcapsules Promote Nerve Regeneration via Mitochondrial Energy Supply. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 22 38037294
2022 Hierarchical MOF-on-MOF Architecture for pH/GSH-Controlled Drug Delivery and Fe-Based Chemodynamic Therapy. Inorganic chemistry 22 35138838
2019 MYST1/KAT8 contributes to tumor progression by activating EGFR signaling in glioblastoma cells. Cancer medicine 22 31691527
2024 KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2. Nature communications 21 38961108
2023 Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance. Cell discovery 21 37460462
2017 Acetylation of hMOF Modulates H4K16ac to Regulate DNA Repair Genes in Response to Oxidative Stress. International journal of biological sciences 21 28808424
2024 MOF-on-MOF Growth: Inducing Naturally Nonpreferred MOFs and Atypical MOF Growth. Accounts of chemical research 19 39388366
2022 Constructing fluorine-doped Zr-MOF films on titanium for antibacteria, anti-inflammation, and osteogenesis. Biomaterials advances 19 35581071
2021 Mixing Mg-MOF-74 with Zn-MOF-74: A Facile Pathway of Controlling the Pharmacokinetic Release Rate of Curcumin. ACS applied bio materials 18 35006987
2020 Estrogen/estrogen receptor promotes the proliferation of endometrial carcinoma cells by enhancing hMOF expression. Japanese journal of clinical oncology 18 31990345
2020 WSTF acetylation by MOF promotes WSTF activities and oncogenic functions. Oncogene 18 32518374
2024 Targeting the KAT8/YEATS4 Axis Represses Tumor Growth and Increases Cisplatin Sensitivity in Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 38526153
2024 Mitochondrial MOF regulates energy metabolism in heart failure via ATP5B hyperacetylation. Cell reports 17 39392752
2024 MOF-mediated PRDX1 acetylation regulates inflammatory macrophage activation. Cell reports 16 39207899
2023 First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8. Journal of medicinal chemistry 16 37155735
2023 The histone acetyltransferase Mof regulates Runx2 and Osterix for osteoblast differentiation. Cell and tissue research 16 37247031
2023 Recent Progress and Future Prospects of Laccase Immobilization on MOF Supports for Industrial Applications. Applied biochemistry and biotechnology 16 37378720
2016 Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation. The Journal of biological chemistry 16 27382063
2013 RNAi screening identifies KAT8 as a key molecule important for cancer cell survival. International journal of clinical and experimental pathology 16 23638218
2023 Monolithic MOF-Based Metal-Insulator-Metal Resonator for Filtering and Sensing. Nano letters 15 36622966
2015 Structure and function of histone acetyltransferase MOF. AIMS biophysics 15 28503659
2023 Rhodium-Based MOF-on-MOF Difunctional Core-Shell Nanoreactor for NAD(P)H Regeneration and Enzyme Directed Immobilization. ACS applied materials & interfaces 14 36609187
2023 hMOF induces cisplatin resistance of ovarian cancer by regulating the stability and expression of MDM2. Cell death discovery 14 37291112
2024 Long-Range Epitaxial MOF Electronics for Continuous Monitoring of Human Breath Ammonia. Journal of the American Chemical Society 13 38291728
2022 Grass Carp (Ctenopharyngodon idella) KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7. Frontiers in immunology 13 35046960
2021 KAT8/MOF-Mediated Anti-Cancer Mechanism of Gemcitabine in Human Bladder Cancer Cells. Biomolecules & therapeutics 13 33041265
2021 KAT8, lysine acetyltransferase 8, is required for adipocyte differentiation in vitro. Biochimica et biophysica acta. Molecular basis of disease 13 33617987
2018 Identification of novel inhibitors of histone acetyltransferase hMOF through high throughput screening. European journal of medicinal chemistry 13 30145373

Missed literature

Know a paper Affinage missed for KAT8? Flag it for the maintainers and the community.

No submissions yet.