Affinage

KAT8

Histone acetyltransferase KAT8 · UniProt Q9H7Z6

Length
458 aa
Mass
52.4 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KAT8 (hMOF/MYST1) is a MYST-family lysine acetyltransferase that serves as a central epigenetic and metabolic regulator through histone acetylation, non-histone protein acetylation, and lysine lactylation across nuclear, cytoplasmic, and mitochondrial compartments. KAT8 operates in two functionally distinct complexes: the MSL complex, which catalyzes bulk H4K16 acetylation to regulate chromatin structure, DNA damage signaling, autophagy gene expression, and X chromosome dosage compensation, and the NSL complex, which catalyzes H4K5/K8 acetylation essential for housekeeping gene transcription initiation and cell viability (PMID:33657400, PMID:24842875, PMID:23863932). Its catalytic mechanism follows a ping-pong kinetic scheme requiring Ac-CoA-driven autoacetylation at K274 for structural stability and enzymatic competence, while its activity is regulated by SIRT1-mediated deacetylation that modulates chromatin recruitment, and by USP10-mediated deubiquitination that controls protein stability (PMID:26505788, PMID:27382063, PMID:21502975, PMID:38317006). Beyond histones, KAT8 acetylates diverse substrates including p53-pathway regulators (DBC1), the antioxidant transcription factor Nrf2, mitochondrial proteins (COX17, ATP5B), and IRF1 via phase-separated condensates to drive PD-L1 transcription, and additionally functions as a pan-lysine lactyltransferase that lactylates substrates such as eEF1A2 to enhance translation elongation and PCK2 to remodel mitochondrial fatty acid synthesis (PMID:24126058, PMID:24571482, PMID:37813994, PMID:39392752, PMID:36894639, PMID:38359291, PMID:39853940).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2005 High

    Establishing that KAT8 functions upstream of ATM in the DNA damage response resolved how H4K16 acetylation is coupled to damage signaling kinase activation.

    Evidence Co-IP of hMOF-ATM, dominant-negative mutant, RNAi, and in vitro kinase assays in human cells after ionizing radiation

    PMID:15923642

    Open questions at the time
    • Direct mechanism by which H4K16ac activates ATM autophosphorylation was not defined
    • Whether this requires the MSL or NSL complex was unknown
  2. 2007 High

    Demonstrating that KAT8 is the primary cellular H4K16 acetyltransferase and that its loss causes pleiotropic genome instability established the foundational substrate specificity and essentiality of the enzyme.

    Evidence RNAi knockdown with cell cycle, chromosome aberration, transcription, and DNA repair phenotypic readouts in human cells

    PMID:17694080

    Open questions at the time
    • Whether other MYST-family members contribute to H4K16ac under specific conditions
    • Mechanism linking H4K16ac loss to G2/M arrest not molecularly defined
  3. 2008 High

    Showing that KAT8-mediated H4K16ac controls nucleosome positioning and transcription at a specific tumor suppressor locus (TMS1/ASC) independently of DNA methylation revealed a direct epigenetic mechanism of gene regulation.

    Evidence siRNA knockdown of hMOF and MSL subunits, ChIP, nucleosome positioning assays in cancer cells

    PMID:18701507

    Open questions at the time
    • Genome-wide scope of H4K16ac-dependent nucleosome positioning was not assessed
    • Whether NSL complex contributes to this locus was untested
  4. 2011 High

    Discovery that KAT8 autoacetylates at K274 and that SIRT1 deacetylates this site to enhance chromatin recruitment established a key regulatory switch controlling KAT8 activity and chromatin engagement.

    Evidence In vitro autoacetylation assay, Co-IP, nucleosome-binding assay, ChIP with SIRT1 KD/OE in HeLa cells

    PMID:21502975

    Open questions at the time
    • Structural basis of how K274 acetylation status alters nucleosome binding was not yet resolved
    • In vivo dynamics of SIRT1-KAT8 regulatory cycle during specific cellular processes
  5. 2013 High

    Identification of DBC1 as a non-histone substrate acetylated by KAT8 at K112/K215, with functional consequences for the SIRT1-DBC1 regulatory axis during DNA damage, expanded KAT8's role beyond histones into signaling pathway modulation.

    Evidence Co-IP, in vitro acetylation, site-directed mutagenesis, SIRT1 deacetylase activity assays

    PMID:24126058

    Open questions at the time
    • Full spectrum of non-histone substrates was unknown
    • Relative contribution of histone vs. non-histone acetylation to DNA damage outcomes
  6. 2013 High

    Genome-wide demonstration that autophagy induction is coupled to KAT8 downregulation and H4K16 deacetylation at autophagy gene promoters established KAT8 as an epigenetic gatekeeper of autophagy.

    Evidence ChIP-seq for H4K16ac, RNA-seq, hMOF KD/OE, cell viability assays

    PMID:23863932

    Open questions at the time
    • Signal transduction pathway by which autophagy triggers KAT8 downregulation was unclear
    • Whether the MSL or NSL complex mediates autophagy-related H4K16ac
  7. 2014 High

    Dissecting MOF's role in MSL-dependent Tsix regulation and NSL-dependent pluripotency maintenance in ESCs revealed complex-specific functions in X chromosome inactivation.

    Evidence Conditional KD, RNA-seq, ChIP-seq, allele-specific expression, RNA FISH in mouse ESCs

    PMID:24842875

    Open questions at the time
    • Whether human X inactivation uses the same complex-specific logic
    • Mechanism by which NSL complex maintains pluripotency genes independently of Tsix
  8. 2015 High

    Kinetic and structural characterization of the KAT8 catalytic mechanism showed a ping-pong reaction where Ac-CoA binds first, and that K274 autoacetylation is structurally essential — crystal structure of K274P mutant revealed disordering of the α2-β7 loop.

    Evidence In vitro enzyme kinetics, ITC, X-ray crystallography, systematic mutagenesis, thermal stability measurements

    PMID:26505788 PMID:27382063

    Open questions at the time
    • Full-length KAT8 structure in complex context (MSL or NSL) unavailable
    • How complex incorporation modulates catalytic parameters
  9. 2016 High

    Discovery that MOF and KANSL3 localize to mitochondria, bind mtDNA, and regulate respiratory gene expression — with conditional KO causing hypertrophic cardiomyopathy — established a dual nuclear-mitochondrial function for KAT8.

    Evidence Subcellular fractionation, mitochondrial import assays, mtDNA ChIP, catalytic mutant rescue, cardiac-specific conditional KO mouse

    PMID:27768893

    Open questions at the time
    • Mechanism of KAT8 mitochondrial import not fully defined
    • Identity of mitochondrial substrates beyond mtDNA binding
  10. 2017 High

    Demonstrating that KAT8 catalytic activity is required for MLL-AF9 and NUP98-HOXA9 leukemia pathogenicity established KAT8 as a therapeutic target in AML.

    Evidence Conditional Mof KO mouse AML model, catalytic mutant rescue failure, RNA-seq, MYST inhibitor treatment

    PMID:28202522

    Open questions at the time
    • Which KAT8 target genes are critical for leukemia maintenance
    • Whether MSL or NSL complex mediates the leukemogenic function
  11. 2017 High

    Oocyte-specific Kat8 deletion causing follicle development failure via ROS accumulation, rescuable by N-acetylcysteine, defined KAT8 as essential for female fertility through direct transcriptional regulation of antioxidant genes.

    Evidence Conditional Kat8 KO (Gdf9-Cre), RNA-seq, ChIP at antioxidant gene promoters, antioxidant rescue

    PMID:28506985

    Open questions at the time
    • Whether KAT8 has additional oocyte-specific substrates beyond antioxidant gene regulation
    • Role of MSL vs. NSL complex in oogenesis
  12. 2018 High

    Showing that MOF depletion causes replication fork slowing, R-loop accumulation, and impaired PCNA recruitment established a direct role for KAT8 in replication stress resolution.

    Evidence DNA fiber assay, Co-IP of MOF-PCNA, immunofluorescence, CHK1 phosphorylation assay, siRNA knockdown

    PMID:29298824

    Open questions at the time
    • Whether MOF directly acetylates PCNA or acts indirectly
    • Mechanism coupling H4K16ac to R-loop resolution
  13. 2020 High

    Identification of MOF as a TNF-α/NF-κB coactivator in macrophages, with elevated MOF/H4K16ac at inflammatory promoters in diabetic wound macrophages, linked KAT8 to innate immune inflammatory transcription.

    Evidence Myeloid-specific conditional KO (Lyz2Cre), ChIP for H4K16ac at inflammatory promoters, wound healing model, pharmacological TNF-α inhibition

    PMID:32069267

    Open questions at the time
    • Direct NF-κB subunit acetylation by MOF not tested
    • Whether NSL complex participates in macrophage inflammatory gene regulation
  14. 2020 High

    Single-cell and ChIP-seq analyses revealed a MOF-RUNX1-GFI1B regulatory network controlling erythroid commitment, with Mof haploinsufficiency causing HSC accumulation rescuable by Gata1 or HDAC inhibition.

    Evidence scRNA-seq, ChIP-seq, conditional Mof deletion, Gata1 genetic rescue, HDAC inhibitor treatment

    PMID:32671208

    Open questions at the time
    • Direct vs. indirect role of MOF in GATA1-dependent erythroid gene activation
    • Whether erythroid defects are MSL or NSL complex-dependent
  15. 2021 High

    Rigorous dissection using auxin-inducible degron showed that KAT8's substrate specificity is complex-dependent — MSL complex drives H4K16ac while NSL complex drives H4K5/K8ac — and that the NSL complex, not H4K16ac, is essential for cell viability and housekeeping gene transcription initiation.

    Evidence Selective complex depletion via auxin-inducible degron, histone modification profiling by MS, ATAC-seq, RNA-seq, ChIP-seq

    PMID:33657400

    Open questions at the time
    • How NSL complex is recruited specifically to housekeeping promoters
    • Structural basis for complex-dependent substrate switching
  16. 2021 High

    Demonstrating that TGFβ-SMAD3 downregulates KAT8 to reduce H4K16ac at autophagy gene promoters, activating autophagy and fibrosis, connected KAT8 to a disease-relevant signaling-epigenetic axis.

    Evidence ChIP for H4K16ac at ATG7/BECLIN1, KD/OE rescue, dermal/pulmonary fibrosis mouse models

    PMID:34285225

    Open questions at the time
    • Whether KAT8 directly acetylates TGFβ-SMAD pathway components
    • Therapeutic efficacy of KAT8 activation in fibrosis
  17. 2023 High

    Discovery that KAT8 undergoes liquid-liquid phase separation with IRF1 to form condensates that acetylate IRF1 K78 and drive PD-L1 transcription revealed a biophysical mechanism for substrate-specific catalysis in immune checkpoint regulation.

    Evidence In vitro droplet formation, Co-IP, ChIP, in vitro acetylation, blocking peptide, tumor models

    PMID:36894639

    Open questions at the time
    • Whether KAT8 forms condensates with other transcription factor partners
    • In vivo dynamics and regulation of KAT8-IRF1 condensates
  18. 2023 High

    Identification of COX17 as a mitochondrial substrate acetylated by the MOF-KANSL complex, with acetylation-mimetic COX17 rescuing respiratory defects in both KO cells and patient fibroblasts, provided a direct mechanistic link from mitochondrial MOF to respiratory chain assembly.

    Evidence Co-IP, in vitro acetylation, electron microscopy, complex IV activity assay, COX17 acetylation-mimetic rescue, patient fibroblast validation

    PMID:37813994

    Open questions at the time
    • Full mitochondrial acetylome of KAT8 beyond COX17 and ATP5B
    • Molecular basis of MOF syndrome in patients
  19. 2023 Medium

    Selective KAT8 inhibitors (compounds 19/34) with confirmed cellular target engagement demonstrated pharmacological tractability of KAT8 for cancer therapy.

    Evidence Biochemical inhibition assay, selectivity panel, CETSA, antiproliferative assays in NSCLC and AML lines

    PMID:37155735

    Open questions at the time
    • In vivo efficacy and pharmacokinetics not reported
    • Selectivity between MSL and NSL complex functions not addressed
  20. 2024 High

    Demonstration that KAT8 is a pan-lysine lactyltransferase — catalyzing lactylation of eEF1A2 to boost translation elongation and of LTBP1 to increase collagen — fundamentally expanded the enzyme's catalytic repertoire beyond acetylation.

    Evidence Global lactylome MS profiling, in vitro lactyltransferase assays, Co-IP, KAT8 KO xenograft model, translation elongation assays

    PMID:38359291 PMID:39102921

    Open questions at the time
    • Structural basis for dual acetyl/lactyl-CoA utilization
    • Full scope of the KAT8-dependent lactylome
    • Whether complex context (MSL/NSL) influences lactyltransferase activity
  21. 2024 High

    Identification of mitochondrial ATP5B K201 acetylation by MOF, opposed by SIRT3, with mtMOF overexpression causing cardiac dysfunction, defined a pathogenic axis of mitochondrial hyperacetylation.

    Evidence Quantitative acetylome MS, in vitro acetylation, mtMOF transgenic and SIRT3 KO mouse models, respiration assays

    PMID:39392752

    Open questions at the time
    • Whether endogenous mitochondrial MOF levels are dynamically regulated
    • How mitochondrial MOF is imported and its import signals
  22. 2024 High

    Showing that KAT8-mediated H4K16ac at the CDX2 promoter is essential for trophoblast stem cell self-renewal, with embryonic lethality upon Kat8 KO rescuable by SIRT1 inhibition, established KAT8 in placental development.

    Evidence Conditional Kat8 KO, CUT&Tag for H4K16ac, CDX2 rescue, EX527 pharmacological rescue, trophoblast organoids

    PMID:38961108

    Open questions at the time
    • Additional trophoblast target genes regulated by KAT8
    • Whether NSL complex function contributes to placental development
  23. 2025 Medium

    Discovery that KAT8 lactylates PCK2 to augment its kinase activity, competitively inhibiting Parkin-mediated OXSM ubiquitination and remodeling mitochondrial fatty acid synthesis, extended KAT8 lactyltransferase function to metabolic stress and ferroptosis.

    Evidence In vitro lactylation assay, Co-IP, PCK2 KO mice, ubiquitination epistasis, mitochondrial metabolic flux analysis

    PMID:39853940

    Open questions at the time
    • Whether lactylation vs. acetylation of the same substrate has distinct outcomes
    • In vivo relevance of KAT8-dependent lactylation in non-ischemic contexts
    • Independent replication needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for KAT8's complex-dependent substrate switching (MSL vs. NSL), how mitochondrial import of KAT8 is regulated, the full scope of the KAT8-dependent lactylome vs. acetylome, and whether the phase separation mechanism extends to other transcription factor partners.
  • No cryo-EM/crystal structure of full KAT8 within MSL or NSL holocomplex
  • Mitochondrial targeting signal and import mechanism remain undefined
  • Genome-wide mapping of KAT8-dependent lactylation not performed
  • Therapeutic window for KAT8 inhibition in cancer vs. normal tissue not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 19 GO:0016740 transferase activity 6 GO:0140110 transcription regulator activity 6 GO:0042393 histone binding 5 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 9 GO:0005694 chromosome 4 GO:0005739 mitochondrion 3
Pathway
R-HSA-4839726 Chromatin organization 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2 R-HSA-69306 DNA Replication 1
Partners
ATMDBC1IRF1KANSL3MSL1PCNASIRT1USP10
Complex memberships
MSL complexNSL complex (MOF-KANSL)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 hMOF (KAT8) physically interacts with ATM protein; hMOF-dependent H4K16 acetylation is required for ATM autophosphorylation, ATM kinase activity, and downstream effector phosphorylation after ionizing radiation, establishing hMOF as an upstream regulator of ATM-mediated DNA damage signaling. Co-immunoprecipitation, dominant-negative mutant expression, RNAi knockdown, in vitro kinase assays Molecular and cellular biology High 15923642
2007 hMOF is the primary H4K16 acetyltransferase in human cells; loss of hMOF causes G2/M arrest, nuclear morphological defects, spontaneous chromosomal aberrations, reduced transcription, and impaired DNA repair after ionizing radiation. RNAi knockdown with cell cycle, chromosome, and DNA repair phenotypic readouts; substrate specificity assays Oncogene High 17694080
2008 hMOF-mediated H4K16 acetylation flanking the TMS1/ASC CpG island is required for nucleosome positioning and active transcription of this tumor suppressor gene; down-regulation of hMOF or MSL complex components decreases H4K16ac, disrupts nucleosome positioning, and silences TMS1 independently of DNA methylation changes. siRNA knockdown, chromatin immunoprecipitation, nucleosome positioning assays, gene expression analysis Cancer research High 18701507
2010 hMOF and SIRT1 have opposing activities on H4K16 acetylation: hMOF acetylates H4K16 while SIRT1 deacetylates it; hMOF overexpression sensitizes multidrug-resistant cancer cells to the topoisomerase II inhibitor etoposide and this effect is antagonized by SIRT1 overexpression. siRNA knockdown, overexpression, western blot for H4K16ac, cell viability assays Oncogene Medium 20118981
2011 hMOF autoacetylates itself at K274 within the MYST domain in vitro and in vivo; SIRT1 deacetylates autoacetylated hMOF through interaction with the MYST domain; non-acetylated hMOF binds nucleosomes more robustly, and SIRT1-mediated deacetylation promotes hMOF recruitment to chromatin and H4K16 acetylation at target genes. In vitro autoacetylation assay, Co-IP, in vitro nucleosome-binding assay, ChIP in HeLa cells with SIRT1 KD/OE Cell research High 21502975
2013 hMOF acetylates DBC1 (CCAR2) at K112 and K215; this acetylation inhibits DBC1 binding to SirT1, thereby increasing SirT1 deacetylase activity; after DNA damage, ATM-dependent inhibition of hMOF binding to DBC1 reduces DBC1 acetylation, promoting SirT1-DBC1 complex formation and influencing cell fate. Co-IP, in vitro acetylation assay, site-directed mutagenesis, SirT1 deacetylase activity assay Molecular and cellular biology High 24126058
2013 hMOF knockdown promotes hepatocellular carcinoma cell growth; mechanistically hMOF regulates expression of SIRT6 and its downstream genes. siRNA knockdown, overexpression, xenograft model, gene expression analysis Biochemical and biophysical research communications Low 25181338
2013 KAT8 regulates G2/M cell cycle arrest through AKT/ERK-cyclin D1 signaling and promotes p53 induction with consequent reduction of Bcl-2 expression upon KAT8 inhibition. RNAi screen, lentiviral KD, cell cycle analysis, western blot for signaling intermediates International journal of clinical and experimental pathology Medium 23638218
2013 Induction of autophagy is coupled to downregulation of hMOF (KAT8) and consequent reduction of H4K16ac; this H4K16 deacetylation predominantly downregulates autophagy-related genes and determines cell survival vs. death outcome during autophagy. hMOF knockdown/overexpression, ChIP-seq for H4K16ac genome-wide, RNA-seq, cell viability assays Nature High 23863932
2014 hMOF physically interacts with and acetylates Nrf2 at Lys588; MOF-mediated Nrf2 acetylation increases nuclear retention of Nrf2 and transcription of its downstream antioxidant/drug-resistance genes. Co-IP, in vitro acetylation assay, site-directed mutagenesis, nuclear fractionation, reporter assays British journal of pharmacology High 24571482
2014 In mouse ESCs, MOF-containing MSL complex specifically regulates Tsix (major Xist repressor) to maintain Xist repression; MSL depletion reduces Tsix expression, decreases REX1 recruitment, and causes ectopic X inactivation; the NSL complex provides Tsix-independent repression of Xist by maintaining pluripotency. Conditional KD, RNA-seq, ChIP-seq, allele-specific expression analysis, RNA FISH eLife High 24842875
2014 MYST1 (MOF/KAT8) costimulates androgen receptor (AR) and NF-κB transcription functions in prostate cancer cells; NF-κB activation promotes SIRT1-dependent deacetylation of MYST1, and mutually exclusive interactions of MYST1 with SIRT1 vs. AR regulate H4K16 acetylation. Co-IP, siRNA knockdown, cell cycle analysis, apoptosis assays, western blot Molecular endocrinology Medium 24702180
2015 KAT8 follows a ping-pong catalytic mechanism in which Ac-CoA binds first followed by the histone substrate; this was validated by enzyme kinetics and isothermal titration calorimetry measuring substrate affinities. In vitro enzyme kinetics, isothermal titration calorimetry (ITC) European journal of medicinal chemistry High 26505788
2015 Arsenic trioxide directly binds hMOF protein (via its C2HC zinc finger) and inhibits its HAT activity in vitro, resulting in reduced global H4K16ac; HDAC4 upregulation by arsenic is not the primary driver of H4K16 deacetylation. Arsenic-immobilized agarose pulldown, in vitro HAT assay, MALDI-TOF mass spectrometry, UV absorption, overexpression rescue experiments PloS one High 26473953
2016 MOF and a subset of NSL complex partners (KANSL3) reside in mitochondria; mitochondrial MOF binds mtDNA in a KANSL3-dependent manner and regulates expression of respiratory genes from both nuclear and mtDNA; a catalytically deficient MOF mutant cannot rescue respiratory or mtDNA transcriptional defects; conditional Mof KO causes hypertrophic cardiomyopathy with severe mitochondrial degeneration. Subcellular fractionation, mitochondrial import assays, mtDNA ChIP, catalytic mutant rescue experiments, cardiac-specific conditional KO mouse model Cell High 27768893
2016 hMOF K274 autoacetylation is required for structural stability and catalytic activity; all amino acid substitutions at K274 destabilize hMOF and abrogate H4 peptide acetylation; crystal structure of K274P mutant reveals disordering of the α2-β7 loop harboring this residue; Ac-CoA binding likely drives K274 autoacetylation prior to cognate substrate acetylation. X-ray crystallography, in vitro acetyltransferase assays, mutational scanning, thermal stability measurements The Journal of biological chemistry High 27382063
2017 KAT8's HAT enzymatic activity (H4K16 acetylation) is required for MLL-AF9 leukemia pathogenicity; catalytically inactive MOF mutants cannot rescue leukemia growth; Mof deletion reduces tumor burden in mouse MLL-AF9 AML model and impairs global H4K16ac; MOF is also required in NUP98-HOXA9-driven AML. Conditional Mof KO mouse model, catalytic mutant rescue, RNA-seq, γH2AX foci, small-molecule MYST inhibitor Cancer research High 28202522
2017 KAT8 is essential for female fertility; oocyte-specific Kat8 deletion causes follicle development failure due to downregulation of antioxidant genes and consequent ROS increase; KAT8 directly binds antioxidant gene promoters as shown by ChIP; N-acetylcysteine antioxidant treatment rescues the follicle development defects. Conditional Kat8 KO (Gdf9-Cre), RNA-seq, ChIP, antioxidant rescue experiment Development High 28506985
2017 Oxidative stress induces SIRT1, which deacetylates hMOF (reducing its chromatin affinity and activity), thereby decreasing H4K16ac and suppressing transcription of DNA repair genes independently of DNA methylation. RNA-seq, RRBS-seq, ChIP, SIRT1 KD/OE in colorectal cancer cells treated with H2O2 International journal of biological sciences Medium 28808424
2017 Drosophila MOF (KAT8 ortholog) is ubiquitylated by MSL2 E3 ligase at multiple lysine residues in vitro; in vivo ubiquitylation sites were mapped by mass spectrometry; mutant MOF derivatives were used to assess functional importance of ubiquitylation for dosage compensation complex formation and X chromosome targeting. Mass spectrometry ubiquitylation mapping, in vitro ubiquitylation assay, site-directed mutagenesis, genetic complementation PloS one Medium 28510597
2018 MOF depletion leads to reduced replication fork speed, increased stalled forks, elevated R-loop formation, and impaired DNA damage repair (reduced Mre11, RPA70, Rad51, PCNA foci, reduced CHK1 phosphorylation); MOF physically interacts with PCNA and affects its ubiquitination and recruitment to DNA damage sites. DNA fiber assay, Co-IP, immunofluorescence foci analysis, CHK1 phosphorylation assay, siRNA knockdown Molecular and cellular biology High 29298824
2020 MOF acts as a coactivator of TNF-α/NF-κB-mediated inflammatory gene transcription in macrophages; myeloid-specific Mof-KO mice have reduced inflammatory cytokine expression; wound macrophages from diabetic obese mice have elevated MOF and H4K16ac on inflammatory gene promoters; TNF-α stimulates MOF expression and etanercept (TNF-α inhibitor) reduces MOF levels. Myeloid-specific conditional KO (Lyz2Cre Moffl/fl), ChIP for H4K16ac at inflammatory promoters, wound healing model, pharmacological inhibition JCI insight High 32069267
2020 MOF influences erythroid fate by dynamic chromatin recruitment; a regulatory network of MOF, RUNX1, and GFI1B controls erythroid commitment; GFI1B activates Mof expression and is necessary and sufficient for cell-type-specific Mof induction; Mof haploinsufficiency causes accumulation of a transient HSC population rescued by Gata1 expression or HDAC inhibition. Single-cell RNA-seq, ChIP-seq, conditional Mof deletion, genetic rescue (Gata1 overexpression), HDAC inhibitor treatment Science advances High 32671208
2020 MOF acetylates WSTF at K426; this acetylation is reversed by SIRT1; MSL1v1 interaction with WSTF facilitates its interaction with MOF for K426 acetylation; WSTF K426 acetylation promotes WSTF Ser158 phosphorylation and enhances WSTF kinase and transcriptional regulatory activities. Co-IP, in vitro acetylation assay, site-directed mutagenesis, kinase activity assay Oncogene Medium 32518374
2021 TGFβ reduces MYST1 (KAT8) expression via SMAD3-dependent transcriptional downregulation, which decreases H4K16ac at autophagy gene promoters (ATG7, BECLIN1), activates autophagy, promotes collagen release, and drives tissue fibrosis; forced MYST1 expression abrogates TGFβ-induced autophagy and fibrosis. siRNA knockdown, MYST1 overexpression, ChIP for H4K16ac, autophagy flux assays, dermal/pulmonary fibrosis mouse models Nature communications High 34285225
2021 KAT8 has complex-dependent catalytic activity: as part of the NSL complex it catalyzes H4K5ac and H4K8ac, whereas as part of the MSL complex it catalyzes bulk H4K16ac; MSL complex/H4K16ac are dispensable for cell proliferation and chromatin accessibility, but NSL complex is essential for cell survival by stimulating transcription initiation at housekeeping gene promoters. Auxin-inducible degron system for selective complex depletion, mass spectrometry for histone modification profiling, ATAC-seq, RNA-seq, ChIP-seq Molecular cell High 33657400
2023 In response to IFNγ, KAT8 undergoes liquid-liquid phase separation with IRF1 to form biomolecular condensates; multivalent specific and promiscuous interactions between IRF1 and KAT8 drive condensate formation; KAT8-IRF1 condensation promotes IRF1 K78 acetylation by KAT8, IRF1 binding to the CD274 (PD-L1) promoter, and PD-L1 transcription; disrupting condensates with a blocking peptide inhibits PD-L1 expression. Phase separation assays (in vitro droplet formation), Co-IP, ChIP, in vitro acetylation, peptide blocking experiments, cell and in vivo tumor models Nature cancer High 36894639
2023 MOF (as part of the MOF-KANSL complex) acetylates COX17 (a mitochondrial complex IV assembly factor); loss of MOF-KANSL complex causes mitochondrial fragmentation, reduced cristae density, and impaired complex IV integrity; expression of acetylation-mimetic COX17 rescues these defects even in absence of MOF; patient fibroblasts with MOF syndrome show respiratory defects rescued by alternative oxidase, acetylation-mimetic COX17, or mitochondrially targeted MOF. Co-IP, in vitro acetylation assay, mitochondrial imaging (electron microscopy), complex IV activity assay, genetic rescue with COX17 acetylation mutants Nature metabolism High 37813994
2023 KAT8 acetylation at K168/175 (catalyzed by GCN5, reversed by SIRT6) reduces KAT8 binding activity and inhibits recruitment of RNA Pol II to promoters of lipolysis genes ATGL and HSL, thereby downregulating lipolysis and affecting invasion/migration of colorectal cancer cells. Co-IP, site-directed mutagenesis of KAT8 K168/175, ChIP for RNA Pol II, lipolysis assays, migration/invasion assays Cell death & disease Medium 36849520
2023 KAT8 acetylates YEATS4 protein, and this acetylation impairs YEATS4 interaction with the E3 ubiquitin ligase HUWE1, preventing YEATS4 ubiquitination and proteasomal degradation; KAT8 inhibition with MG149 reduces YEATS4 acetylation and sensitizes bladder cancer cells to cisplatin. Co-IP, ubiquitination assay, acetylation assay, KAT8 inhibitor (MG149) treatment, CRISPR screen Advanced science Medium 38526153
2023 KAT8 catalyzes lysine butyrylation (Kbu) of HSP90 at K754 (as writer), while HDAC11 acts as eraser; SDCBP increases Kbu level by competing with HDAC11; HSP90 K754 Kbu upregulates HSP90 expression and contributes to chemoresistance in ESCC. Butyrylome mass spectrometry profiling, Co-IP, gain/loss-of-function, competitive binding assays Cell discovery Medium 37460462
2023 First-in-class selective KAT8 inhibitors (compounds 19 and 34) were identified; cellular target engagement confirmed by CETSA; both inhibitors reduce H4K16ac and display antiproliferative activity in NSCLC and AML cell lines without affecting non-transformed cells. Biochemical KAT8 inhibition assay, selectivity panel against other KATs/KDACs, western blot, immunofluorescence, CETSA Journal of medicinal chemistry Medium 37155735
2024 KAT8 functions as a pan-lysine lactyltransferase (Kla writer): it installs lactyl marks on multiple protein substrates, including eEF1A2 at K408; eEF1A2 K408 lactylation boosts translation elongation and enhances protein synthesis to promote colorectal cancer tumorigenesis; KAT8 deletion inhibits tumor growth, especially in a high-lactate microenvironment. Global lactylome profiling (MS), Co-IP for KAT8-eEF1A2 interaction, in vitro lactyltransferase assay, KAT8 KO mouse xenograft model, translation elongation assays Proceedings of the National Academy of Sciences of the United States of America High 38359291
2024 USP10 deubiquitinase binds to and deubiquitinates MOF at K410, protecting it from proteasomal degradation; MOF stabilization by USP10 promotes H4K16ac enrichment at the ANXA2 promoter in a JUN-dependent manner, activating ANXA2 transcription and downstream Wnt/β-catenin signaling in esophageal squamous cell cancer. Co-IP, ubiquitination assay, CHX chase assay, ChIP for H4K16ac, catalytic mutant (MOF-E350Q) rescue experiment Oncogene High 38317006
2024 KAT8 mediates lactylation of LTBP1 at K752 in fibroblasts, and this modification increases collagen I and III protein levels; fibroblasts uptake extracellular lactate via MCT1 to support this KAT8-dependent lactylation. Co-IP, in vitro lactylation assay, MCT1 inhibition, western blot for collagen levels International journal of biological macromolecules Medium 39102921
2024 Mitochondria-localized MOF acetylates ATP5B at K201; co-regulation of ATP5B K201 acetylation by MOF (writer) and SIRT3 (eraser) impairs mitochondrial respiration and ATP synthesis; overexpression of mitochondria-targeted MOF (mtMOF) in mice causes mitochondrial dysfunction, cardiac remodeling, and heart failure; SIRT3 KO aggravates mtMOF-induced damage. Quantitative acetylome MS, Co-IP, in vitro acetylation assay, mtMOF transgenic/KO mouse models, mitochondrial respiration assays Cell reports High 39392752
2024 KAT8-mediated H4K16ac at the CDX2 promoter is essential for trophoblast stem cell self-renewal and proliferation; trophoblast-specific Kat8 KO causes extraembryonic ectoderm abnormalities and embryonic lethality; CDX2 overexpression partially rescues Kat8 KO defects; SIRT1 inhibitor EX527 restores CDX2 levels and placental development. Conditional Kat8 KO, RNA-seq, CUT&Tag for H4K16ac at CDX2 locus, CDX2 rescue, EX527 pharmacological rescue, trophoblast organoids Nature communications High 38961108
2025 Lactate-primed KAT8 directly lactylates PCK2 at Lys100, augmenting PCK2 kinase activity; lactylated PCK2 competitively inhibits Parkin-mediated polyubiquitination of OXSM, leading to remodeling of mitochondrial fatty acid synthesis and potentiation of ferroptosis during hepatic ischemia/reperfusion injury. In vitro lactylation assay, Co-IP, gene-edited mice (PCK2 KO), ubiquitination assay, mitochondrial metabolic flux analysis Advanced science Medium 39853940

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 677 28451673
2013 The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy. Nature 270 23863932
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 202 38359291
2005 Involvement of human MOF in ATM function. Molecular and cellular biology 186 15923642
2016 MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria. Cell 148 27768893
2020 Enzyme embedded metal organic framework (enzyme-MOF): De novo approaches for immobilization. International journal of biological macromolecules 127 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 113 17694080
2016 Design and Synthesis of a Water-Stable Anionic Uranium-Based Metal-Organic Framework (MOF) with Ultra Large Pores. Angewandte Chemie (International ed. in English) 105 27440749
2023 MOF-On-MOF Dual Enzyme-Mimic Nanozyme with Enhanced Cascade Catalysis for Colorimetric/Chemiluminescent Dual-Mode Aptasensing. Analytical chemistry 101 37427434
2023 Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity. Nature cancer 98 36894639
2023 MOF-derived bimetallic nanozyme to catalyze ROS scavenging for protection of myocardial injury. Theranostics 96 37215581
2020 pH-sensitive MOF integrated with glucose oxidase for glucose-responsive insulin delivery. Journal of controlled release : official journal of the Controlled Release Society 88 31978443
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
2014 MOF-associated complexes ensure stem cell identity and Xist repression. eLife 81 24842875
2021 TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy. Nature communications 78 34285225
2021 Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis. Molecular cell 77 33657400
2020 Covalent Graphene-MOF Hybrids for High-Performance Asymmetric Supercapacitors. Advanced materials (Deerfield Beach, Fla.) 76 33274794
2023 Understanding MOF Flexibility: An Analysis Focused on Pillared Layer MOFs as a Model System. Angewandte Chemie (International ed. in English) 75 37052183
2009 Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure. Toxicology and applied pharmacology 71 19732783
2008 Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity. Cancer research 70 18701507
2010 Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide. Oncogene 69 20118981
2023 Self-assembly of colloidal metal-organic framework (MOF) particles. Chemical Society reviews 68 36930224
2021 Natural Polymers Decorated MOF-MXene Nanocarriers for Co-delivery of Doxorubicin/pCRISPR. ACS applied bio materials 68 35007059
2016 The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis. International journal of molecular sciences 66 26784169
2023 Photodynamic Alginate Zn-MOF Thermosensitive Hydrogel for Accelerated Healing of Infected Wounds. ACS applied materials & interfaces 65 37129874
2023 Augmenting Immunotherapy via Bioinspired MOF-Based ROS Homeostasis Disruptor with Nanozyme-Cascade Reaction. Advanced materials (Deerfield Beach, Fla.) 65 37689996
2018 GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness. Small (Weinheim an der Bergstrasse, Germany) 65 30091524
2020 Tip-To-Middle Anisotropic MOF-On-MOF Growth with a Structural Adjustment. Journal of the American Chemical Society 63 31968935
2011 Modulations of hMOF autoacetylation by SIRT1 regulate hMOF recruitment and activities on the chromatin. Cell research 57 21502975
2022 MOFs and MOF-Derived Materials for Antibacterial Application. Journal of functional biomaterials 55 36412856
2024 MOFs and MOF-Based Composites as Next-Generation Materials for Wound Healing and Dressings. Small (Weinheim an der Bergstrasse, Germany) 53 38453672
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
2023 Multi-Bioinspired MOF Delivery Systems from Microfluidics for Tumor Multimodal Therapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 49 37852943
2019 Electrostatically Assembling 2D Nanosheets of MXene and MOF-Derivatives into 3D Hollow Frameworks for Enhanced Lithium Storage. Small (Weinheim an der Bergstrasse, Germany) 48 31588685
2013 Histone acetyltransferase hMOF promotes S phase entry and tumorigenesis in lung cancer. Cellular signalling 47 23628702
2024 Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing. Journal of nanobiotechnology 45 38575979
2020 TNF-α regulates diabetic macrophage function through the histone acetyltransferase MOF. JCI insight 44 32069267
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) 42 28506985
2023 Current status and prospects of MIL-based MOF materials for biomedicine applications. RSC medicinal chemistry 40 37859709
2019 MOF-Based Nanotubes to Hollow Nanospheres through Protein-Induced Soft-Templating Pathways. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 40 30937262
2015 Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells. PloS one 39 26473953
2024 Ultrasound Trigger Ce-Based MOF Nanoenzyme For Efficient Thrombolytic Therapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 38576170
2023 Enhanced Bioactivity of Enzyme/MOF Biocomposite via Host Framework Engineering. Journal of the American Chemical Society 37 37671920
2024 MOF-Derived Nanoparticles with Enhanced Acoustical Performance for Efficient Mechano-Sonodynamic Therapy. Advanced materials (Deerfield Beach, Fla.) 34 38896775
2021 MOF@COF Heterostructure Hybrid for Dual-Mode Photoelectrochemical-Electrochemical HIV-1 DNA Sensing. Langmuir : the ACS journal of surfaces and colloids 34 34734735
2014 The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth. Biochemical and biophysical research communications 34 25181338
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 32 39102921
2014 Coactivator MYST1 regulates nuclear factor-κB and androgen receptor functions during proliferation of prostate cancer cells. Molecular endocrinology (Baltimore, Md.) 32 24702180
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) 31 39853940
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 28 31943753
2023 COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function. Nature metabolism 27 37813994
2020 Temporal expression of MOF acetyltransferase primes transcription factor networks for erythroid fate. Science advances 27 32671208
2015 Enzyme kinetics and inhibition of histone acetyltransferase KAT8. European journal of medicinal chemistry 27 26505788
2019 Paper-based microfluidic devices for glucose assays employing a metal-organic framework (MOF). Analytica chimica acta 26 30782373
2018 MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks. Molecular and cellular biology 26 29298824
2025 Mannosylated MOF Encapsulated in Lactobacillus Biofilm for Dual-Targeting Intervention Against Mammalian Escherichia coli Infections. Advanced materials (Deerfield Beach, Fla.) 25 40277329
2021 Role of histone acetyltransferases MOF and Tip60 in genome stability. DNA repair 24 34399315
2020 Recent advances in fluorescence sensors based on DNA-MOF hybrids. Luminescence : the journal of biological and chemical luminescence 24 32064758
2020 miR-149-5p inhibition reduces Alzheimer's disease β-amyloid generation in 293/APPsw cells by upregulating H4K16ac via KAT8. Experimental and therapeutic medicine 24 32973937
2016 Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition. Cancer biology & therapy 23 27715462
2022 Hierarchical MOF-on-MOF Architecture for pH/GSH-Controlled Drug Delivery and Fe-Based Chemodynamic Therapy. Inorganic chemistry 22 35138838
2013 hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1. Molecular and cellular biology 22 24126058
2024 Stabilization of MOF (KAT8) by USP10 promotes esophageal squamous cell carcinoma proliferation and metastasis through epigenetic activation of ANXA2/Wnt signaling. Oncogene 21 38317006
2023 KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells. Cell death & disease 21 36849520
2017 Acetylation of hMOF Modulates H4K16ac to Regulate DNA Repair Genes in Response to Oxidative Stress. International journal of biological sciences 21 28808424
2023 Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance. Cell discovery 19 37460462
2022 Constructing fluorine-doped Zr-MOF films on titanium for antibacteria, anti-inflammation, and osteogenesis. Biomaterials advances 19 35581071
2020 Exploring the Tunability of Trimetallic MOF Nodes for Partial Oxidation of Methane to Methanol. ACS applied materials & interfaces 19 32427460
2024 KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2. Nature communications 18 38961108
2023 Ligand-Screened Cerium-Based MOF Microcapsules Promote Nerve Regeneration via Mitochondrial Energy Supply. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 38037294
2021 Mixing Mg-MOF-74 with Zn-MOF-74: A Facile Pathway of Controlling the Pharmacokinetic Release Rate of Curcumin. ACS applied bio materials 17 35006987
2020 Estrogen/estrogen receptor promotes the proliferation of endometrial carcinoma cells by enhancing hMOF expression. Japanese journal of clinical oncology 17 31990345
2018 The immobilization of Candida rugosa lipase on the modified polyethersulfone with MOF nanoparticles as an excellent performance bioreactor membrane. Journal of biotechnology 17 30458213
2015 MOF-templated rough, ultrathin inorganic microcapsules for enzyme immobilization. Journal of materials chemistry. B 17 32262795
2024 Targeting the KAT8/YEATS4 Axis Represses Tumor Growth and Increases Cisplatin Sensitivity in Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 38526153
2023 First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8. Journal of medicinal chemistry 16 37155735
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
2024 Mitochondrial MOF regulates energy metabolism in heart failure via ATP5B hyperacetylation. Cell reports 15 39392752
2023 The histone acetyltransferase Mof regulates Runx2 and Osterix for osteoblast differentiation. Cell and tissue research 15 37247031
2021 Harnessing Shape Complementarity for Upgraded Cyclohexane Purification through Adaptive Bottlenecked Pores in an Imidazole-Containing MOF. Angewandte Chemie (International ed. in English) 15 34463419
2020 WSTF acetylation by MOF promotes WSTF activities and oncogenic functions. Oncogene 15 32518374
2019 Sulfonated Sub-Nanochannels in a Robust MOF Membrane: Harvesting Salinity Gradient Power. ACS applied materials & interfaces 15 31469536
2018 TopoFF: MOF structure prediction using specifically optimized blueprints. Faraday discussions 15 30028457
2015 Structure and function of histone acetyltransferase MOF. AIMS biophysics 15 28503659
2023 Monolithic MOF-Based Metal-Insulator-Metal Resonator for Filtering and Sensing. Nano letters 14 36622966
2023 hMOF induces cisplatin resistance of ovarian cancer by regulating the stability and expression of MDM2. Cell death discovery 13 37291112
2024 Long-Range Epitaxial MOF Electronics for Continuous Monitoring of Human Breath Ammonia. Journal of the American Chemical Society 12 38291728
2024 Bioreaction-Compatible Bivariate Lanthanide MOF Sensor Enables Stimulus-Multiresponsive Platform for ctDNA On-Site Detection. Analytical chemistry 12 38922180
2022 Grass Carp (Ctenopharyngodon idella) KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7. Frontiers in immunology 12 35046960
2017 Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster. PloS one 12 28510597
2015 Identification of acetyltransferase genes (HAT1 and KAT8) regulating HBV replication by RNAi screening. Cell & bioscience 12 26640654
2022 Linker Deprotonation and Structural Evolution on the Pathway to MOF-74. Inorganic chemistry 11 35254060
2022 Construction and evaluation of detachable bone-targeting MOF carriers for the delivery of proteasome inhibitors. RSC advances 11 35702207
2020 Pt-Ni@PC900 Hybrid Derived from Layered-Structure Cd-MOF for Fuel Cell ORR Activity. ACS omega 11 32064373
2018 Jolly green MOF: confinement and photoactivation of photosystem I in a metal-organic framework. Nanoscale advances 11 36132458
2016 A multifaceted role for MOF histone modifying factor in genome maintenance. Mechanisms of ageing and development 11 27038808