Affinage

KAT2A

Histone acetyltransferase KAT2A · UniProt Q92830

Length
837 aa
Mass
93.9 kDa
Annotated
2026-04-28
100 papers in source corpus 45 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KAT2A (GCN5) is a versatile lysine acyltransferase that serves as the catalytic subunit of the SAGA and ATAC coactivator complexes, integrating metabolic acyl-CoA pools with chromatin-based gene regulation in development, immunity, and cancer. Within these complexes, the Ada2 subunit allosterically enhances KAT2A activity by promoting acetyl-CoA binding (PMID:30224453), and KAT2A acetylates histone H3 primarily at K9 and K14—with its bromodomain reading H3K14ac to license subsequent H3K18ac—as well as histone variant H2A.Z.1 (PMID:25106422, PMID:31527837). Beyond acetylation, KAT2A functions as a succinyltransferase (H3K79 succinylation via nuclear α-KGDH-supplied succinyl-CoA, controlled by active-site residue Y645) and as a lactyltransferase (histone H3 lactylation using lactyl-CoA generated by nuclear ACSS2), and it acylates non-histone substrates including TFEB, α-tubulin, EGR2, VCP, PKM2, and influenza NP (PMID:29211711, PMID:39561764, PMID:31750630, PMID:31878840, PMID:28723564, PMID:38145956). KAT2A is essential for mouse embryogenesis—loss causes dorsal mesoderm failure and extensive apoptosis—and in the immune system it is required for IL-2-driven T cell responses and iNKT cell development; its stability is regulated by autophagy through a conserved LIR domain (PMID:11017084, PMID:28424240, PMID:31878840).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Establishing that GCN5 and ADA2 form a physical complex that functions together in transcriptional activation answered how GCN5 is organized within coactivator machinery, laying the foundation for understanding SAGA-type complexes.

    Evidence Two-hybrid, co-immunoprecipitation, and double-mutant epistasis in yeast

    PMID:7957049

    Open questions at the time
    • Stoichiometry and full subunit composition of the native complex unknown at this stage
    • Mechanism by which Ada2 stimulates GCN5 activity not addressed
  2. 2000 High

    Demonstrating that Gcn5l2 knockout is embryonic lethal with dorsal mesoderm failure established KAT2A as an essential developmental gene and revealed functional overlap with PCAF.

    Evidence Germline and conditional knockout mice; double Gcn5l2/Pcaf nulls

    PMID:11017084

    Open questions at the time
    • Target genes and histone marks responsible for the mesoderm phenotype unidentified
    • Cell-type autonomy of KAT2A requirement in mesoderm not resolved
  3. 2001 High

    Showing that E2F transcription factors recruit KAT2A/TRRAP and require GCN5 catalytic activity for transactivation identified a key transcription-factor-dependent recruitment mechanism.

    Evidence Co-IP, catalytic mutant, and transactivation assays in human cells

    PMID:11418595

    Open questions at the time
    • Genome-wide target sites of E2F-GCN5 co-occupancy not mapped
    • Whether E2F recruits SAGA vs. ATAC complex not distinguished
  4. 2003 High

    Crystal structures of Gcn5 with histone H4 and p53 peptides defined how the HAT domain accommodates divergent substrates through a common lysine-binding mechanism with variable N-terminal contacts, explaining both histone and non-histone substrate recognition.

    Evidence X-ray crystallography of Tetrahymena Gcn5 with peptide substrates plus in vitro acetyltransferase assays

    PMID:14661947

    Open questions at the time
    • Structures with nucleosomal substrates lacking
    • Selectivity determinants within full-length human KAT2A not addressed
  5. 2008 High

    Biochemical purification resolved KAT2A as a shared catalytic subunit of two distinct human complexes—STAGA/SAGA and ATAC—with different subunit compositions and transcriptional roles, clarifying the organizational logic of GCN5-containing coactivators.

    Evidence Tandem affinity purification, mass spectrometry, co-IP, and in vitro transcription from human cells

    PMID:18838386

    Open questions at the time
    • How cells partition KAT2A between SAGA and ATAC not understood
    • Genomic loci preferentially regulated by ATAC vs. SAGA not distinguished
  6. 2014 High

    Revealing that the GCN5 bromodomain reads its own H3K14ac product to license H3K18ac established an intra-molecular reader-writer crosstalk that orders multi-site acetylation on H3.

    Evidence Quantitative mass spectrometry and in vitro HAT assays with bromodomain-mutant ADA subcomplex

    PMID:25106422

    Open questions at the time
    • In vivo relevance of sequential acetylation on chromatin not tested
    • Whether this crosstalk operates similarly within ATAC and SAGA not compared
  7. 2017 High

    Discovery that KAT2A functions as a histone succinyltransferase—with α-KGDH supplying nuclear succinyl-CoA and Y645 determining acyl-CoA selectivity—expanded the enzyme's catalytic repertoire beyond acetylation and linked metabolic intermediates to epigenetic marks.

    Evidence 2.3 Å crystal structure with succinyl-CoA, Y645A mutagenesis, in vitro succinylation, ChIP, and tumor models

    PMID:29211711

    Open questions at the time
    • How succinyl-CoA nuclear availability is regulated not fully understood
    • Genome-wide distribution of H3K79 succinylation beyond candidate loci not mapped
  8. 2017 High

    Conditional T cell–specific Gcn5 knockout and iNKT studies showed KAT2A is required for IL-2 transcription (via NFAT-directed H3K9ac at the Il2 promoter) and for iNKT cell development (via EGR2 acetylation), establishing cell-type-specific immune functions.

    Evidence Conditional Lck-Cre KO mice, ChIP, co-IP, in vitro acetyltransferase assays, and cytokine/differentiation assays

    PMID:28424240 PMID:28723564

    Open questions at the time
    • Downstream EGR2 acetylation sites' structural effects unresolved
    • Relative contributions of SAGA vs. ATAC in T cell gene regulation unknown
  9. 2018 High

    Structural determination of the Ada2 SANT domain–Gcn5 interface showed Ada2 allosterically enhances acetyl-CoA binding rather than histone substrate binding, resolving a long-standing question about how complex assembly activates the catalytic subunit.

    Evidence Fab-assisted crystal structure of yeast Ada2/Gcn5 complex plus biochemical binding and HAT assays

    PMID:30224453

    Open questions at the time
    • Whether the same allosteric mechanism operates in human ADA2a vs. ADA2b paralog contexts not tested
    • Structural basis for the stronger stimulation by ADA2b than ADA2a not explained
  10. 2019 High

    Multiple studies converged to show KAT2A acetylates non-histone substrates—TFEB (inhibiting autophagy/lysosome gene transcription), α-tubulin (stabilizing microtubules), and H2A.Z.1 (licensing promoter activation via BRD2 recruitment)—demonstrating breadth of substrate scope in distinct cellular contexts.

    Evidence In vitro acetyltransferase assays, mutagenesis, co-IP, ChIP, Drosophila genetics, and cell migration assays

    PMID:31527837 PMID:31750630 PMID:31878840

    Open questions at the time
    • Full acetylome of KAT2A not systematically catalogued
    • Structural basis for H2A.Z.1 vs. H2A.Z.2 discrimination not resolved at atomic level
  11. 2019 High

    Identification of the LIR domain in KAT2A revealed that autophagy directly degrades KAT2A via LC3 interaction, establishing a post-translational regulatory axis that links cellular stress to KAT2A protein levels and tubulin acetylation.

    Evidence LIR domain mutagenesis, autophagy flux assays, ULK1 KO mice with KAT2A siRNA rescue, neointima models

    PMID:31878840 PMID:33985412

    Open questions at the time
    • Whether autophagy-mediated degradation affects nuclear KAT2A pools and histone acetylation equally
    • Ubiquitin signals directing KAT2A to autophagosomes not identified
  12. 2020 High

    Conditional Kat2a loss in AML reduced transcriptional burst frequency and increased gene expression variability, shifting leukemia stem cells toward differentiation—providing a mechanistic explanation for KAT2A's role in maintaining malignant self-renewal programs.

    Evidence Conditional KO in AML, ChIP-seq, ATAC-seq, single-cell RNA-seq

    PMID:31985402

    Open questions at the time
    • Which specific KAT2A-deposited marks (H3K9ac vs. others) are rate-limiting for burst frequency unknown
    • Whether transcriptional noise phenotype is shared across solid tumors not tested
  13. 2020 Medium

    Crystal structure of the KAT2A N-terminal PCAF_N domain revealed a novel E3 ubiquitin ligase fold with a binuclear zinc region, supported by in vitro ubiquitination activity, suggesting a dual enzymatic function beyond acyltransferase activity.

    Evidence 1.8 Å crystal structure plus in vitro ubiquitination assay with UbcH5

    PMID:32820047

    Open questions at the time
    • Physiological substrates of the E3 ligase activity not identified
    • In vivo relevance of ubiquitination activity not demonstrated
    • Independent validation of E3 ligase function needed
  14. 2023 Medium

    A series of studies showed KAT2A succinylates non-histone substrates (VCP-K658, PKM2-K475, CTBP1-K46/K280, PGAM1-K161) to modulate mitophagy, glycolysis, and transcriptional repression, extending the succinyltransferase function well beyond histones.

    Evidence Co-IP, site-directed mutagenesis at target lysines, enzymatic activity assays, and xenograft models across multiple cancer cell types

    PMID:36764210 PMID:37294531 PMID:38145956 PMID:38835015

    Open questions at the time
    • Most findings from single laboratories awaiting independent replication
    • Selectivity rules for succinylation vs. acetylation of non-histone substrates not defined
    • In vitro reconstitution with purified proteins not shown for all substrates
  15. 2024 High

    Discovery that ACSS2 generates lactyl-CoA and partners with KAT2A to lactylate histone H3—regulated by EGFR-ERK signaling—added a third acyl-CoA species to KAT2A's catalytic repertoire, linking growth-factor signaling to a new epigenetic mark.

    Evidence Co-crystal structure of KAT2A with lactyl-CoA, co-IP, in vitro lactylation, ERK phosphorylation assay, tumor and immune models

    PMID:39561764

    Open questions at the time
    • Genome-wide distribution of KAT2A-dependent histone lactylation not mapped
    • Whether lactylation and succinylation compete at the same active site under physiological conditions not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KAT2A partitions among acetyl-CoA, succinyl-CoA, and lactyl-CoA acylation reactions in vivo—and how metabolic flux, complex assembly (SAGA vs. ATAC), and post-translational modifications (sumoylation, autophagic degradation) combinatorially control substrate and acyl-donor selectivity—remains an open integrative question.
  • No systematic in vivo quantification of the relative acylation outputs
  • Structural basis for SAGA-ATAC differential targeting still incomplete
  • Full spectrum of KAT2A-dependent acylation marks across the proteome and chromatin not catalogued

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 15 GO:0016740 transferase activity 10 GO:0140110 transcription regulator activity 7 GO:0042393 histone binding 5
Localization
GO:0005634 nucleus 7 GO:0005694 chromosome 5
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-4839726 Chromatin organization 6 R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3 R-HSA-1266738 Developmental Biology 2
Partners
ACSS2ADA2AADA2BE2F1EGR2NFATTFEBTRRAP
Complex memberships
ATACSAGA (STAGA)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 KAT2A (GCN5) acts as a histone H3 succinyltransferase: the α-ketoglutarate dehydrogenase (α-KGDH) complex localizes to the nucleus, binds KAT2A at gene promoters, and provides succinyl-CoA as substrate. Crystal structure of KAT2A catalytic domain in complex with succinyl-CoA at 2.3 Å shows succinyl-CoA binds a deep cleft with the succinyl moiety pointing toward a flexible loop 3; Y645 in this loop determines selective binding of succinyl-CoA over acetyl-CoA. KAT2A succinylates histone H3K79 near transcription start sites, promoting gene expression and tumor cell proliferation. Crystal structure (2.3 Å), site-directed mutagenesis (Y645A), in vitro succinylation assay, ChIP, nuclear fractionation, cell proliferation and tumor growth assays Nature High 29211711
2024 ACSS2 functions as a lactyl-CoA synthetase that converts lactate to lactyl-CoA; it forms a complex with KAT2A after EGFR-ERK-mediated S267 phosphorylation and nuclear translocation. KAT2A then acts as a lactyltransferase to lactylate histone H3, driving Wnt/β-catenin, NF-κB, and PD-L1 expression. Co-crystal structure demonstrates lactyl-CoA binding to KAT2A. Co-crystal structure, Co-IP, in vitro lactylation assay, ERK phosphorylation assay, tumor growth and immune evasion models Cell metabolism High 39561764
1994 GCN5 (KAT2A yeast ortholog) physically interacts with ADA2 in a heteromeric complex that mediates transcriptional activation; double-mutant studies show ADA2 and GCN5 function together in the same complex or pathway. The GCN5 bromodomain is functionally important for a general activity of transcription factors but is not required for the GCN5-ADA2 interaction. Two-hybrid assay, co-immunoprecipitation, double-mutant epistasis analysis The EMBO journal High 7957049
2000 Gcn5l2 (mouse ortholog of KAT2A) is essential for embryogenesis: knockout embryos die with failure to form dorsal mesoderm (chordamesoderm and paraxial mesoderm) and exhibit extensive apoptosis; Pcaf-null mice are viable, but Gcn5l2/Pcaf double nulls are more severely affected, indicating overlapping functions. Conditional and germline knockout mouse (null embryos), histology, apoptosis assays Nature genetics High 11017084
2008 Human KAT2A (GCN5) is a subunit of two distinct multiprotein complexes: STAGA (~2 MDa, containing SPT3, TAF9, TRRAP) and ATAC (~700 kDa, containing ADA2a, ADA3, STAF36, WDR5, POLE3/CHRAC17, POLE4, TAK1/MAP3K7, MBIP, YEATS2-NC2β). The ATAC YEATS2-NC2β module interacts with TBP and negatively regulates transcription when recruited to a promoter. Biochemical purification, mass spectrometry, Co-IP, in vitro transcription assay The Journal of biological chemistry High 18838386
2018 The Ada2 SANT domain activates Gcn5 HAT activity by enhancing Gcn5 binding to the enzymatic cosubstrate acetyl-CoA, rather than by affecting histone peptide binding. Crystal structures of the yeast Ada2/Gcn5 complex with Fab chaperones reveal the structural basis of this allosteric mechanism. Crystal structure (Fab-assisted crystallization), biochemical HAT assays, binding measurements Proceedings of the National Academy of Sciences of the United States of America High 30224453
2003 Crystal structures of Tetrahymena Gcn5 bound to histone H4 and p53 peptides reveal that the Gcn5/PCAF HAT family accommodates divergent substrates by using analogous interactions with the target lysine and two C-terminal residues, while N-terminal substrate residues provide enhanced affinity for histone H3 specifically. X-ray crystallography, in vitro acetyltransferase assays Biochemistry High 14661947
2014 The bromodomain of Gcn5 regulates site specificity of HAT activity on histone H3: bromodomain-mutant ADA subcomplex (Gcn5-Ada2-Ada3) shows severely diminished H3K18ac; H3K14ac by Gcn5 and subsequent bromodomain binding to H3K14ac are prerequisite steps for H3K18ac, revealing cross-talk between the Gcn5 reader and writer functions. Quantitative mass spectrometry, acid-urea gel, in vitro HAT assays with wild-type and bromodomain mutant complexes Molecular & cellular proteomics : MCP High 25106422
2015 Subunits of either ATAC (ADA2a-containing) or SAGA (ADA2b-containing) HAT modules stimulate GCN5 acetyltransferase activity on histone H3, primarily at H3K14; ADA2b has a stronger stimulatory effect than ADA2a; incorporation of HAT modules into holo-complexes further increases activity without changing lysine specificity. In vitro HAT assays with purified recombinant and endogenous complexes, histone peptide and full-length histone substrates The Journal of biological chemistry High 26468280
2007 GCN5 (KAT2A) is recruited by c-Myc to RNA polymerase III-transcribed genes (tRNA, 5S rRNA) together with TRRAP, leading to selective H3 (but not H4) hyperacetylation, increased TFIIIB occupancy, and transcriptional induction. ChIP, inducible Myc system, ChIP-qPCR, RT-PCR Proceedings of the National Academy of Sciences of the United States of America High 17848523
2001 E2F-1 and E2F-4 transactivation domains bind KAT2A (GCN5) and cofactor TRRAP in vivo; catalytically active GCN5 is required for E2F-mediated transactivation and histone acetyltransferase activity recruited by E2F-4 in vivo. Co-IP, transactivation assays, HAT activity assays with wild-type and catalytic mutants, domain-mapping mutations The Journal of biological chemistry High 11418595
2019 KAT2A (GCN5) acetylates TFEB (master transcription factor for autophagy/lysosome genes) at K274 and K279, reducing TFEB transcriptional activity by disrupting TFEB dimerization and promoter binding; autophagy induction inactivates GCN5 and reduces TFEB acetylation, increasing lysosome formation. In vitro acetyltransferase assay, Co-IP, site-directed mutagenesis, autophagy flux assays, Drosophila genetic model EMBO reports High 31750630
2019 KAT2A mediates H3K79 succinylation at the YWHAZ (14-3-3ζ) promoter to upregulate 14-3-3ζ expression; KAT2A Y645A (succinyltransferase-defective) mutant reduces H3K79 succinylation and 14-3-3ζ levels, leading to decreased β-catenin stability and reduced glycolysis and proliferation in pancreatic cancer cells. ChIP-qPCR, site-directed mutagenesis (Y645A), immunoprecipitation, western blot, cell proliferation and glycolysis assays Cancer letters High 31610265
2019 KAT2A (GCN5) directly acetylates α-tubulin (TUBA) in vascular smooth muscle cells; autophagic degradation of KAT2A via a conserved LC3-interacting region (LIR) domain reduces TUBA acetylation, destabilizes microtubules, and promotes directional VSMC migration. Co-IP, GST pulldown, LIR domain mutagenesis, autophagy flux assays, cell migration assays, in vitro acetyltransferase assay Autophagy High 31878840
2021 ULK1 deletion inhibits autophagic degradation of KAT2A, causing KAT2A accumulation, increased α-tubulin acetylation, microtubule stabilization, and inhibition of VSMC directional migration and neointima formation; local KAT2A siRNA in ulk1 KO mice reverses the protective effect. Vascular smooth muscle cell-specific Ulk1 KO mouse, carotid artery ligation model, KAT2A siRNA, western blot, immunofluorescence, migration assays Autophagy High 33985412
2017 GCN5 (KAT2A) is recruited to the il-2 promoter by interacting with NFAT upon TCR stimulation in T cells, catalyzing H3K9 acetylation (not NFAT acetylation directly) to promote IL-2 transcription; conditional T cell-specific Gcn5 KO impairs IL-2 production, T cell proliferation, and Th1/Th17 differentiation. Conditional Lck-Cre Gcn5 KO mouse, ChIP, Co-IP (GCN5-NFAT), T cell proliferation and cytokine assays Journal of immunology High 28424240
2017 GCN5 (KAT2A) is the specific lysine acetyltransferase of EGR2 transcription factor; GCN5-mediated acetylation positively regulates EGR2 transcriptional activity, and this activity is required for iNKT cell development through Runx1, PLZF, IL-2Rβ, and T-bet transcription. In vitro acetyltransferase assay, Co-IP, conditional KO mouse, pharmacological GCN5 inhibition, gene expression analysis Cell reports High 28723564
2004 GCN5 directly binds TGF-β-specific R-Smads and BMP-specific R-Smads (the latter unlike PCAF), acts as a transcriptional coactivator enhancing TGF-β and BMP signaling-induced transcription; GCN5 knockdown by RNAi represses TGF-β-induced transcriptional activity. Biochemical purification from nuclear extract using Smad-binding DNA element, Co-IP, reporter gene assays, RNAi knockdown Genes to cells : devoted to molecular & cellular mechanisms Medium 15009097
2016 The lncRNA GClnc1 acts as a molecular scaffold bridging WDR5 and KAT2A complexes, coordinating their localization to target gene promoters (including SOD2) and specifying the histone modification pattern to promote gastric cancer cell biology. RNA immunoprecipitation, Co-IP, ChIP, RNA pulldown, functional assays in gastric cancer models Cancer discovery Medium 27147598
2019 lncRNA PVT1 serves as a scaffold for KAT2A, enabling KAT2A-mediated H3K9 acetylation at the NF90 promoter, which recruits TIF1β to activate NF90 transcription and increase HIF-1α stability; KAT2A acetyltransferase activity-deficient mutants fail to promote PVT1-mediated NPC cell proliferation. RNA-IP, ChIP, KAT2A catalytic mutant expression, siRNA knockdown, rescue experiments, xenograft model Cell death and differentiation Medium 31320749
2007 GCN5 (Drosophila ortholog) acetylates the nucleosome remodeling ATPase ISWI at K753 (equivalent to H3K14) in vivo and in vitro; the target sequence on ISWI is similar to the H3 N-terminus recognized by GCN5, suggesting co-regulation of a remodeler and its substrate through related epitopes. In vitro acetyltransferase assay, mass spectrometry, immunoprecipitation, site-directed mutagenesis BMC molecular biology Medium 17760996
2019 KAT2A (GCN5) acetylates histone variant H2A.Z.1 (but not H2A.Z.2, due to alanine-14 in H2A.Z.2 inhibiting KAT2A activity) at promoters of transactivated genes; the DNA repair complex XPC-RAD23-CEN2 interacts with H2A.Z and KAT2A to recruit KAT2A to promoters and license H2A.Z.1 acetylation, which then recruits BRD2 to promote RNA Pol II recruitment. In vitro acetyltransferase assay, Co-IP, ChIP, H2A.Z.1 acetylation-deficient mutant, RNAi knockdown Nature chemical biology High 31527837
2020 Kat2a loss in AML cells reduces transcriptional burst frequency at a subset of gene promoters, generating enhanced transcriptional variability; this destabilization of target gene programs shifts leukemia cell fate from self-renewal to differentiation, depleting leukemia stem-like cells. Conditional Kat2a knockout mouse, chromatin profiling (ChIP-seq, ATAC-seq), single-cell RNA-seq, transcription factor binding analysis eLife High 31985402
2018 KAT2A (GCN5) histone acetyltransferase maintains ATRA resistance in non-APL AML via aberrant H3K9 acetylation, sustaining stemness and leukemia-associated gene expression; GCN5 inhibition combined with LSD1 inhibition unlocks ATRA-driven differentiation across most non-APL AML subtypes. Pharmacological GCN5 inhibition, ChIP (H3K9ac), gene expression analysis, differentiation assays, in vivo models Leukemia Medium 31576004
2020 GCN5 (KAT2A) promotes transcription of MYC-induced cell-cycle genes as an essential coactivator; deletion of Gcn5 in the Eμ-Myc B-cell lymphoma mouse model delays or abrogates tumorigenesis and reduces Myc expression and downstream functions. Conditional Gcn5 KO in Eμ-Myc mouse model, ChIP-seq, gene expression analysis, survival studies Cancer research High 33168647
2011 And-1 (acidic nucleoplasmic DNA-binding protein) forms a complex with both histone H3 and GCN5, stabilizing GCN5 protein; And-1 knockdown causes GCN5 proteasomal degradation, reducing H3K9 and H3K56 acetylation; And-1 overexpression stabilizes GCN5 through protein-protein interactions. Co-IP, siRNA knockdown, western blot (H3K9ac, H3K56ac), proteasome inhibitor rescue Oncogene Medium 21725360
2006 GCN5 (yeast ortholog) is sumoylated at K25 in vivo; while sumoylation in vitro does not affect HAT activity, constitutive SUMO fusion to GCN5 N-terminus causes defective growth on 3-AT media and reduced transcription of SAGA-dependent gene TRP3. In vitro sumoylation assay, site-directed mutagenesis, SUMO-fusion expression, growth assay, reporter gene assay Biochemistry Medium 16411780
2014 GCN5 physically interacts with CDK5 and acetylates it at Lys33 within the ATP binding domain; GCN5 and CDK5 co-localize at specific nuclear foci. Co-IP, fluorescent localization, LC-MS/MS identification of acetylation site Biochemical and biophysical research communications Medium 24704205
2017 KAT2A (GCN5) promotes BMSC-mediated angiogenesis by enhancing H3K9ac levels at the Vegf promoter; GCN5 declines in BMSCs from osteoporotic bone, reducing proangiogenic capacity; GCN5 overexpression by lentiviral vector restores angiogenesis in ovariectomized mice. ChIP (H3K9ac at Vegf promoter), siRNA knockdown, GCN5 overexpression, in vivo lentiviral rescue, tube formation assay FASEB journal Medium 28642327
2022 KAT2A promotes HBV transcription by binding to cccDNA through interaction with HBV core protein (HBc), and catalyzes H3K79 succinylation on cccDNA-associated histones; KAT2A silencing specifically reduces cccDNA-bound succinylated H3K79 without affecting cccDNA production. ChIP-seq (cccDNA ChIP), Co-IP (KAT2A-HBc), siRNA knockdown, HBV-infected cell and mouse models Frontiers in microbiology Medium 35140694
2023 KAT2A mediates succinylation of VCP at K658, inhibiting VCP-MFN1 interaction and suppressing mitophagy in BMSCs; TNF-α induces KAT2A expression, and KAT2A-mediated VCP succinylation impedes BMMSC quiescence. Co-IP, succinylation assay, site-directed mutagenesis (K658), mitophagy assays, in vivo fracture model Advanced science Medium 38145956
2023 KAT2A promotes succinylation of PKM2 at K475 in gastric cancer cells, reducing PKM2 activity (not protein levels), thereby promoting glycolysis and cancer progression; KAT2A directly interacts with PKM2. Co-IP, immunofluorescence co-localization, succinylation immunoprecipitation, pyruvate kinase activity assay, site-directed mutagenesis (K475), rescue experiments Molecular biotechnology Medium 37294531
2023 KAT2A promotes succinylation of CTBP1 at K46 and K280; succinylation of CTBP1 suppresses its inhibitory activity on CDH1 transcription, promoting prostate cancer progression. Co-IP, succinylation assay, site-directed mutagenesis, luciferase reporter assay, in vivo xenograft Biochemical and biophysical research communications Medium 36764210
2018 GCN5 (KAT2A) acetylates influenza A virus nucleoprotein (NP) at K90 in vitro; GCN5 silencing decreases viral polymerase activity, while PCAF silencing (acetylating K31) increases it, indicating opposing roles of these acetyltransferases on NP function. In vitro acetyltransferase assay, MS identification of acetylation sites, RNAi knockdown, viral polymerase activity assay The Journal of biological chemistry Medium 29555684
2020 KAT2A (GCN5) acts as a histone malonyltransferase: KAT2A knockdown reduces global histone malonylation levels; SIRT5 deacylase selectively removes malonylation from histones; H2B_K5 is a highly malonylated site regulated by SIRT5. siRNA knockdown of all 22 KATs, mass spectrometry, SIRT5 deacylase assay, malonyl-CoA supplementation iScience Medium 36879797
2020 KAT2A stabilizes pluripotency gene regulatory networks in mouse embryonic stem cells by controlling transcriptional heterogeneity; Kat2a inhibition increases transcriptional variability of pluripotency-associated genes and accelerates mesendodermal differentiation. KAT2A inhibition (pharmacological), single-cell transcriptomics, gene regulatory network analysis, differentiation assays Stem cells Medium 30270482
2021 KAT2A (GCN5) directly acetylates TUBA/α-tubulin, increasing microtubule stability; autophagic degradation of KAT2A reduces TUBA acetylation, and KAT2A accumulation (in Ulk1 KO VSMCs) increases acetylated TUBA, inhibiting directional migration and neointima formation. In vivo Ulk1 KO mouse + KAT2A siRNA rescue, western blot for acetyl-TUBA, migration assay, carotid artery ligation model Autophagy Medium 33985412
2024 KAT2A (Kat2a) promotes ferroptosis in diabetic cardiomyopathy by increasing H3K27ac and H3K9ac enrichment at the Tfrc and Hmox1 promoters, upregulating their expression; Kat2a expression itself is regulated post-transcriptionally by m6A methylation via ALKBH5 (demethylase) and YTHDF2 (m6A reader that promotes Kat2a mRNA degradation). ChIP-qPCR, siRNA knockdown, in vitro and in vivo DCM models, m6A methylation assays, RIP Cell death & disease Medium 38858351
2022 KAT2A (GCN5) suppresses NRF2 activity in macrophages, supporting H3K9 acetylation and limiting NRF2-mediated transcriptional repression of proinflammatory genes (Il1b, Nlrp3); KAT2A facilitates macrophage glycolysis reprogramming and licenses NLRP3 inflammasome activation. KAT2A siRNA and pharmacological inhibition (MB-3), ChIP (H3K9ac), NRF2 activity assay, collagen-induced arthritis mouse model, NLRP3 inflammasome activation assay MedComm Medium 37313329
2024 KAT2A promotes succinylation of PGAM1 at K161, regulating glycolysis in hepatocellular carcinoma; KAT2A directly interacts with PGAM1; astragaloside IV suppresses this KAT2A-PGAM1 succinylation axis. Co-IP, immunofluorescence, succinylation-IP, site-directed mutagenesis (K161), xenograft tumor model BMC cancer Medium 38835015
2020 GCN5 (KAT2A) crystal structure of PCAF_N domain at 1.8 Å reveals a helical structure with a binuclear zinc region that constitutes a new class of E3 ligase fold; GCN5 exhibits ubiquitination activity supported by UbcH5. Crystal structure (1.8 Å), in vitro ubiquitination assay The Journal of biological chemistry Medium 32820047
2018 GCN5 (KAT2A) interacts with ATM upon doxorubicin treatment in early drug-resistant leukemia cells; GCN5 facilitates ATM recruitment to DNA double-strand break sites, hyperactivating ATM and downstream repair factors (H2AX, NBS1, BRCA1, Chk2, Mcl-1), promoting DNA repair and cell survival; GCN5 inhibition reduces ATM activation. Co-IP (GCN5-ATM), ChIP (ATM at DSB sites), pharmacological inhibition, western blot, cell viability assays International journal of cancer Medium 29297932
2022 KAT2A cooperates with E2F1 and is recruited to the UBE2C promoter by E2F1, increasing H3K9 acetylation and UBE2C expression to promote cancer cell proliferation and migration. ChIP, Co-IP, immunofluorescence co-localization, RNA-seq, functional proliferation and migration assays Genes Medium 36292703
2024 GCN5 (KAT2A) deposits H3K9ac onto WNT gene promoters and enhancers (e.g., WNT7A, WNT7B, WNT10A, WNT4) as part of the E2F1/4-pRb/RBL2-GCN5 axis, regulating CSC self-renewal, chemoresistance, and invasiveness in pancreatic and breast cancer. Quantitative proteomics, ChIP, siRNA knockdown, functional assays in CSC models, epistasis analysis Nature communications Medium 38678032
2017 GCN5 (KAT2A) is required for expression of multiple FGF signaling pathway components during early embryoid body differentiation; Gcn5-null EBs show deficient ERK and p38 activation, cytoskeletal mislocalization, and impaired mesodermal differentiation; GCN5 directly targets four cMYC target genes among seven identified by genomic analysis. Gcn5 KO embryoid body system, ChIP-seq, gene expression analysis, signaling pathway assays Stem cell reports Medium 29249668
2023 ALDOB enters the nucleus and interacts with KAT2A, leading to inhibition of H3K9 acetylation at the TGFB1 promoter, suppressing TGF-β1 transcription; ALDOB deficiency releases this suppression, increasing TGF-β and enabling immune evasion in HCC. Nuclear fractionation, Co-IP (ALDOB-KAT2A), ChIP (H3K9ac at TGFB1 promoter), KAT2A small molecule inhibition, in vivo tumor models Hepatology Medium 38051951

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase. Nature 427 29211711
2016 LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern. Cancer discovery 334 27147598
2007 Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene 314 17694077
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