Acetyltransferase in cardiovascular disease and aging

Abstract

Acetyltransferases are enzymes that catalyze the transfer of an acetyl group to a substrate, a modification referred to as acetylation. Loss-of-function variants in genes encoding acetyltransferases can lead to congenital disorders, often characterized by intellectual disability and heart and muscle defects. Their activity is influenced by dietary nutrients that alter acetyl coenzyme A levels, a key cofactor. Cardiovascular diseases, including ischemic, hypertensive, and diabetic heart diseases - leading causes of mortality in the elderly - are largely attributed to prolonged lifespan and the growing prevalence of metabolic syndrome. Acetyltransferases thus serve as a crucial link between lifestyle modifications, cardiometabolic disease, and aging through both epigenomic and non-epigenomic mechanisms. In this review, we discuss the roles and relevance of acetyltransferases. While the sirtuin family of deacetylases has been extensively studied in longevity, particularly through fasting-mediated NAD⁺ metabolism, recent research has brought attention to the essential roles of acetyltransferases in health and aging-related pathways, including cell proliferation, DNA damage response, mitochondrial function, inflammation, and senescence. We begin with an overview of acetyltransferases, classifying them by domain structure, including canonical and non-canonical lysine acetyltransferases, N-terminal acetyltransferases, and sialic acid O-acetyltransferases. We then discuss recent advances in understanding acetyltransferase-related pathologies, particularly focusing on cardiovascular disease and aging, and explore their potential therapeutic applications for promoting health in older individuals.

Keywords

Acetyltransferase / acetylation / lysine acetyltransferase / KAT / acetyl coenzyme A / deacetylase / cardiovascular disease / aging / diet

References

[1] Martin SS,Almarzooq ZI.2024 heart disease and stroke statistics: a report of US and global data from the american heart association.Circulation2024;149:e347-913

[2] Nakamura M.Cardiomyopathy in obesity, insulin resistance and diabetes.J Physiol2020;598:2977-93

[3] Nakamura M.Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy.J Pharm Pharm Sci2024;27:12568 PMCID:PMC11066298

[4] Afshin A,Reitsma MB.Health effects of overweight and obesity in 195 countries over 25 years.N Engl J Med2017;377:13-27 PMCID:PMC5477817

[5] Pietrocola F,Bravo-San Pedro JM,Kroemer G.Acetyl coenzyme A: a central metabolite and second messenger.Cell Metab2015;21:805-21

[6] Nakamura M,Sadoshima J.Overview of pyridine nucleotides review series.Circ Res2012;111:604-10 PMCID:PMC3523884

[7] Narita T,Choudhary C.Functions and mechanisms of non-histone protein acetylation.Nat Rev Mol Cell Biol2019;20:156-74

[8] Shvedunova M.Modulation of cellular processes by histone and non-histone protein acetylation.Nat Rev Mol Cell Biol2022;23:329-49

[9] Schumacher B,Vijg J.The central role of DNA damage in the ageing process.Nature2021;592:695-703 PMCID:PMC9844150

[10] Allis CD,Cote J.New nomenclature for chromatin-modifying enzymes.Cell2007;131:633-6

[11] Tessarz P.Histone core modifications regulating nucleosome structure and dynamics.Nat Rev Mol Cell Biol2014;15:703-8

[12] Brownell JE.Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation.Curr Opin Genet Dev1996;6:176-84

[13] Kouzarides T.Chromatin modifications and their function.Cell2007;128:693-705

[14] Borrow J,Andresen JM.The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.Nat Genet1996;14:33-41

[15] Kennedy J,Blair E.KAT6A syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.Genet Med2019;21:850-60 PMCID:PMC6634310

[16] Dreveny I,Fulton J.The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification.Nucleic Acids Res2014;42:822-35 PMCID:PMC3902925

[17] Rokudai S,Arnal SM,Kitabayashi I.MOZ increases p53 acetylation and premature senescence through its complex formation with PML.Proc Natl Acad Sci USA2013;110:3895-900 PMCID:PMC3593914

[18] Rokudai S,Tagata Y,Taya Y.Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest.J Biol Chem2009;284:237-44

[19] Katsumoto T,Iwama A.MOZ is essential for maintenance of hematopoietic stem cells.Genes Dev2006;20:1321-30 PMCID:PMC1472906

[20] Perez-Campo FM,Kouskoff V.The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors.Blood2009;113:4866-74 PMCID:PMC2686138

[21] Thomas T,Gugasyan R.Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells.Genes Dev2006;20:1175-86 PMCID:PMC1472476

[22] Voss AK,Dixon MP.Moz and retinoic acid coordinately regulate H3K9 acetylation, Hox gene expression, and segment identity.Dev Cell2009;17:674-86

[23] Newman DM,Lun A.Acetylation of the Cd8 locus by KAT6A determines memory T cell diversity.Cell Rep2016;16:3311-21

[24] Liu Y,Yang J.KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3.Sci Adv2024;10:eadm9326 PMCID:PMC11100567

[25] Champagne N,Pelletier N.Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein.J Biol Chem1999;274:28528-36

[26] Klein BJ,Lachance C.Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation.Nat Commun2019;10:4724 PMCID:PMC6797804

[27] Kraft M,Voss AK.Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice.J Clin Invest2011;121:3479-91 PMCID:PMC3163944

[28] Thomas T,Chowdhury K.Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development.Development2000;127:2537-48

[29] Clayton-Smith J,Daly S.Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.Am J Hum Genet2011;89:675-81 PMCID:PMC3213399

[30] Campeau PM,Lu JT.Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome.Am J Hum Genet2012;90:282-9 PMCID:PMC3276659

[31] Bergamasco MI,Garnham AL.Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice.J Clin Invest2024;134:e167672 PMCID:PMC10977983

[32] Bergamasco MI,Abeysekera W.The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function.Stem Cell Rep2024;19:469-85 PMCID:PMC11096436

[33] Kamine J,Subramanian T,Chinnadurai G.Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator.Virology1996;216:357-66

[34] Yamamoto T.Novel substrate specificity of the histone acetyltransferase activity of HIV-1-Tat interactive protein Tip60.J Biol Chem1997;272:30595-8

[35] Kimura A.Tip60 acetylates six lysines of a specific class in core histones in vitro.Genes Cells1998;3:789-800

[36] Tang Y,Zhang W.Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis.Mol Cell2006;24:827-39

[37] Patel JH,Ard PG.The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60.Mol Cell Biol2004;24:10826-34 PMCID:PMC533976

[38] Hu Y,Koprowski S,Kim MS.Homozygous disruption of the Tip60 gene causes early embryonic lethality.Dev Dyn2009;238:2912-21 PMCID:PMC2801416

[39] Shibahara D,Kobayashi IS.TIP60 is required for tumorigenesis in non-small cell lung cancer.Cancer Sci2023;114:2400-13 PMCID:PMC10236639

[40] Gorrini C,Luise C.Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response.Nature2007;448:1063-7

[41] Ikura T,Grigoriev M.Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.Cell2000;102:463-73

[42] Stilling RM,Benito E.K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation.EMBO J2014;33:1912-27 PMCID:PMC4195786

[43] Urban I,Sakib MS.TIP60/KAT5 is required for neuronal viability in hippocampal CA1.Sci Rep2019;9:16173 PMCID:PMC6838100

[44] Tominaga K,Kasashima K.Tip60/KAT5 histone acetyltransferase is required for maintenance and neurogenesis of embryonic neural stem cells.Int J Mol Sci2023;24:2113 PMCID:PMC9916716

[45] Humbert J,Makrythanasis P.De novo KAT5 variants cause a syndrome with recognizable facial dysmorphisms, cerebellar atrophy, sleep disturbance, and epilepsy.Am J Hum Genet2020;107:564-74 PMCID:PMC7477011

[46] Hilfiker A,Pannuti A.mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila.EMBO J1997;16:2054-60 PMCID:PMC1169808

[47] Taylor GC,Hekimoglu-Balkan B,Bickmore WA.H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction.Genome Res2013;23:2053-65 PMCID:PMC3847775

[48] Sykes SM,Holbert MA.Acetylation of the p53 DNA-binding domain regulates apoptosis induction.Mol Cell2006;24:841-51 PMCID:PMC1766330

[49] Chen Z,Tang N.The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer.Br J Pharmacol2014;171:3196-211 PMCID:PMC4080974

[50] Zhou Y,Mayer C,Akhtar A.Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing.Nat Cell Biol2009;11:1010-6

[51] Huai W,Wang C.KAT8 selectively inhibits antiviral immunity by acetylating IRF3.J Exp Med2019;216:772-85 PMCID:PMC6446880

[52] Thomas T,Voss AK.The genes coding for the MYST family histone acetyltransferases, Tip60 and Mof, are expressed at high levels during sperm development.Gene Expr Patterns2007;7:657-65

[53] Thomas T,Kueh AJ.Mof (MYST1 or KAT8) is essential for progression of embryonic development past the blastocyst stage and required for normal chromatin architecture.Mol Cell Biol2008;28:5093-105 PMCID:PMC2519697

[54] Gupta A,Sharma GG.The mammalian ortholog of Drosophila MOF that acetylates histone H4 lysine 16 is essential for embryogenesis and oncogenesis.Mol Cell Biol2008;28:397-409 PMCID:PMC2223300

[55] Valerio DG,Eisold ME,Pandita TK.Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.Blood2017;129:48-59 PMCID:PMC5216264

[56] Rodrigues CP, Akhtar A. Differential H4K16ac levels ensure a balance between quiescence and activation in hematopoietic stem cells.Sci Adv2021;7:eabi5987 PMCID:PMC8346211

[57] Li L,Weisz-Hubshman M.Lysine acetyltransferase 8 is involved in cerebral development and syndromic intellectual disability.J Clin Invest2020;130:1431-45 PMCID:PMC7269600

[58] Iizuka M.Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein.J Biol Chem1999;274:23027-34

[59] Kueh AJ,Voss AK.HBO1 is required for H3K14 acetylation and normal transcriptional activity during embryonic development.Mol Cell Biol2011;31:845-60 PMCID:PMC3028655

[60] Iizuka M,Mizzen CA.Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers.Gene2009;436:108-14 PMCID:PMC2674512

[61] Iizuka M,Takisawa H.Regulation of replication licensing by acetyltransferase Hbo1.Mol Cell Biol2006;26:1098-108 PMCID:PMC1347032

[62] Kueh AJ,Tang L.HBO1 (KAT7) does not have an essential role in cell proliferation, DNA replication, or histone 4 acetylation in human cells.Mol Cell Biol2020;40:e00506-19 PMCID:PMC6996278

[63] Kueh AJ,Quaglieri A.Stem cell plasticity, acetylation of H3K14, and de novo gene activation rely on KAT7.Cell Rep2023;42:111980

[64] Yang Y,Grant ZL.The histone lysine acetyltransferase HBO1 (KAT7) regulates hematopoietic stem cell quiescence and self-renewal.Blood2022;139:845-58

[65] MacPherson L,Yeung MM.HBO1 is required for the maintenance of leukaemia stem cells.Nature2020;577:266-70

[66] Frontini-López YR,Del Veliz S,Bustos DM.14-3-3β isoform is specifically acetylated at Lys51 during differentiation to the osteogenic lineage.J Cell Biochem2021;122:1767-80

[67] Zou C,Smith RM.SCF(Fbxw15) mediates histone acetyltransferase binding to origin recognition complex (HBO1) ubiquitin-proteasomal degradation to regulate cell proliferation.J Biol Chem2013;288:6306-16 PMCID:PMC3585065

[68] Kleff S,Anderson CW.Identification of a gene encoding a yeast histone H4 acetyltransferase.J Biol Chem1995;270:24674-7

[69] Parthun MR,Gottschling DE.The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism.Cell1996;87:85-94

[70] Verreault A,Kobayashi R.Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase.Curr Biol1998;8:96-108

[71] Ai X.The nuclear Hat1p/Hat2p complex: a molecular link between type B histone acetyltransferases and chromatin assembly.Mol Cell2004;14:195-205

[72] Nagarajan P,Sirbu B.Histone acetyl transferase 1 is essential for mammalian development, genome stability, and the processing of newly synthesized histones H3 and H4.PLoS Genet2013;9:e1003518 PMCID:PMC3675013

[73] Garcia PA, Nagarajan P, Parthun MR. Hat1-dependent lysine acetylation targets diverse cellular functions.J Proteome Res2020;19:1663-73 PMCID:PMC7328124

[74] Yang XJ,Nishikawa J,Nakatani Y.A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A.Nature1996;382:319-24

[75] Georgakopoulos T.Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription.EMBO J1992;11:4145-52 PMCID:PMC556924

[76] Chen L,Si X.Lysine acetyltransferase GCN5 potentiates the growth of non-small cell lung cancer via promotion of E2F1, cyclin D1, and cyclin E1 expression.J Biol Chem2013;288:14510-21 PMCID:PMC3656305

[77] Lerin C,Kalume DE,Pandey A.GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha.Cell Metab2006;3:429-38

[78] Sharabi K,Tavares CDJ.Selective chemical inhibition of PGC-1α gluconeogenic activity ameliorates type 2 diabetes.Cell2017;169:148-60.e15 PMCID:PMC5398763

[79] Xu W,Evrard YA,Behringer RR.Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development.Nat Genet2000;26:229-32

[80] Yamauchi T,Kuwata T.Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis.Proc Natl Acad Sci USA2000;97:11303-6 PMCID:PMC17195

[81] Nguyen MU,Potgieter S.KAT2A and KAT2B prevent double-stranded RNA accumulation and interferon signaling to maintain intestinal stem cell renewal.Sci Adv2024;10:eadl1584 PMCID:PMC11305398

[82] Bararia D,Welner RS.Acetylation of C/EBPα inhibits its granulopoietic function.Nat Commun2016;7:10968 PMCID:PMC4814574

[83] Domingues AF,Giotopoulos G.Loss of Kat2a enhances transcriptional noise and depletes acute myeloid leukemia stem-like cells.Elife2020;9:e51754 PMCID:PMC7039681

[84] Ouyang C,Lu Q.Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/α-tubulin acetylation.Autophagy2020;16:1753-70 PMCID:PMC8386598

[85] Schiltz RL,Vassilev A,Allis CD.Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.J Biol Chem1999;274:1189-92

[86] Sakaguchi K,Saito S.DNA damage activates p53 through a phosphorylation-acetylation cascade.Genes Dev1998;12:2831-41 PMCID:PMC317174

[87] Liu L,Trievel RC.p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage.Mol Cell Biol1999;19:1202-9 PMCID:PMC116049

[88] Maurice T,Meunier J.Altered memory capacities and response to stress in p300/CBP-associated factor (PCAF) histone acetylase knockout mice.Neuropsychopharmacology2008;33:1584-602 PMCID:PMC2459231

[89] Wei W,Li X.p300/CBP-associated factor selectively regulates the extinction of conditioned fear.J Neurosci2012;32:11930-41 PMCID:PMC3466419

[90] Kamei Y,Heinzel T.A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.Cell1996;85:403-14

[91] Lundblad JR,Laurance ME,Goodman RH.Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP.Nature1995;374:85-8

[92] Arany Z,Oldread E,Eckner R.A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.Nature1995;374:81-4

[93] Kasper LH,Biesen MA.Conditional knockout mice reveal distinct functions for the global transcriptional coactivators CBP and p300 in T-cell development.Mol Cell Biol2006;26:789-809 PMCID:PMC1347027

[94] Rebel VI,Tanner EA,Bronson RT.Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal.Proc Natl Acad Sci USA2002;99:14789-94 PMCID:PMC137497

[95] Tanaka Y,Maekawa T,Shiroishi T.Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome.Proc Natl Acad Sci USA1997;94:10215-20 PMCID:PMC23342

[96] Yao TP,Fuchs M.Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.Cell1998;93:361-72

[97] Jin Q,Wang L.Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation.EMBO J2011;30:249-62 PMCID:PMC3025463

[98] Krämer OH,Knauer SK.Acetylation of Stat1 modulates NF-kappaB activity.Genes Dev2006;20:473-85 PMCID:PMC1369049

[99] Cohen HY,Bitterman KJ.Acetylation of the C terminus of Ku70 by CBP and PCAF controls bax-mediated apoptosis.Mol Cell2004;13:627-38

[100] Tanaka Y,Hongo T.Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein.Mech Dev2000;95:133-45

[101] Oike Y,Mamiya T.Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism.Hum Mol Genet1999;8:387-96

[102] Teufel DP,Bycroft M.Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53.Proc Natl Acad Sci USA2007;104:7009-14 PMCID:PMC1855428

[103] Zhong J,Bohrer LR.p300 acetyltransferase regulates androgen receptor degradation and PTEN-deficient prostate tumorigenesis.Cancer Res2014;74:1870-80 PMCID:PMC3971883

[104] Perkins ND,Betts JC,Beach DH.Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator.Science1997;275:523-7

[105] Dikstein R,Tjian R.TAFII250 is a bipartite protein kinase that phosphorylates the base transcription factor RAP74.Cell1996;84:781-90

[106] Mizzen CA,Kokubo T.The TAF_II250 subunit of TFIID has histone acetyltransferase activity.Cell1996;87:1261-70

[107] Jacobson RH,King DS.Structure and function of a human TAFII250 double bromodomain module.Science2000;288:1422-5

[108] Li HH,Sheppard HM.Phosphorylation on Thr-55 by TAF1 mediates degradation of p53: a role for TAF1 in cell G1 progression.Mol Cell2004;13:867-78

[109] Morinière J,Steuerwald U.Cooperative binding of two acetylation marks on a histone tail by a single bromodomain.Nature2009;461:664-8

[110] Chen X,Wu Z.Structural insights into preinitiation complex assembly on core promoters.Science2021;372:eaba8490

[111] O'Rawe JA,Dörfel MJ.TAF1 variants are associated with dysmorphic features, intellectual disability, and neurological manifestations.Am J Hum Genet2015;97:922-32 PMCID:PMC4678794

[112] Aneichyk T,Yadav R.Dissecting the causal mechanism of X-linked dystonia-parkinsonism by integrating genome and transcriptome assembly.Cell2018;172:897-909.e21

[113] Cheng H,Wakeling E.Missense variants in TAF1 and developmental phenotypes: challenges of determining pathogenicity.Hum Mutat2019;449-64

[114] Janakiraman U,Moutal A.TAF1-gene editing alters the morphology and function of the cerebellum and cerebral cortex.Neurobiol Dis2019;132:104539 PMCID:PMC7197880

[115] Crombie EM,Cleverley K.Taf1 knockout is lethal in embryonic male mice and heterozygous females show weight and movement disorders.Dis Model Mech2024;17:dmm050741 PMCID:PMC11261634

[116] Wittschieben BO,Du W,Svejstrup JQ.Overlapping roles for the histone acetyltransferase activities of SAGA and elongator in vivo.EMBO J2000;19:3060-8 PMCID:PMC203375

[117] Creppe C,Volvert ML.Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin.Cell2009;136:551-64

[118] Lin TY,Zakrzewski K.The elongator subunit Elp3 is a non-canonical tRNA acetyltransferase.Nat Commun2019;10:625 PMCID:PMC6367351

[119] Simpson CL,Miskiewicz K.Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration.Hum Mol Genet2009;18:472-81 PMCID:PMC2638803

[120] Bento-Abreu A,Swinnen B.Elongator subunit 3 (ELP3) modifies ALS through tRNA modification.Hum Mol Genet2018;27:1276-89 PMCID:PMC6159532

[121] Dumay-Odelot H,Durrieu-Gaillard S.Identification, molecular cloning, and characterization of the sixth subunit of human transcription factor TFIIIC.J Biol Chem2007;282:17179-89

[122] Martin FJ,Aneja A.Ensembl 2023.Nucleic Acids Res2023;51:D933-41

[123] UniProt Consortium. UniProt: the universal protein knowledgebase in 2023.Nucleic Acids Res2023;51:D523-31

[124] Hsieh YJ,Wang Z,Roeder RG.The TFIIIC90 subunit of TFIIIC interacts with multiple components of the RNA polymerase III machinery and contains a histone-specific acetyltransferase activity.Mol Cell Biol1999;19:7697-704 PMCID:PMC84812

[125] Xu J,O’Malley BW.Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family.Nat Rev Cancer2009;9:615-30 PMCID:PMC2908510

[126] Xu J.Review of the in vivo functions of the p160 steroid receptor coactivator family.Mol Endocrinol2003;17:1681-92

[127] Heery DM,Hoare S.A signature motif in transcriptional co-activators mediates binding to nuclear receptors.Nature1997;387:733-6

[128] Oñate SA,Tsai MJ.Sequence and characterization of a coactivator for the steroid hormone receptor superfamily.Science1995;270:1354-7

[129] Spencer TE,Burcin MM.Steroid receptor coactivator-1 is a histone acetyltransferase.Nature1997;389:194-8

[130] Voegel JJ,Zechel C,Gronemeyer H.TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors.EMBO J1996;15:3667-75 PMCID:PMC452006

[131] Gehin M,Dennefeld C,Gronemeyer H.The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP.Mol Cell Biol2002;22:5923-37 PMCID:PMC133972

[132] Chopra AR,Saha P.Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke’s disease.Science2008;322:1395-9 PMCID:PMC2668604

[133] Picard F,Annicotte J.SRC-1 and TIF2 control energy balance between white and brown adipose tissues.Cell2002;111:931-41

[134] Guan XY,Anzick SL,Trent JM.Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer .Cancer Res1996;56:3446-50

[135] Chen H,Schiltz RL.Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.Cell1997;90:569-80

[136] Doi M,Sassone-Corsi P.Circadian regulator CLOCK is a histone acetyltransferase.Cell2006;125:497-508

[137] Hirayama J,Grimaldi B.CLOCK-mediated acetylation of BMAL1 controls circadian function.Nature2007;450:1086-90

[138] Schauer R.Chapter One - Exploration of the sialic acid world.Adv Carbohydr Chem Biochem2018;75:1-213 PMCID:PMC7112061

[139] Visser EA,Timmermans SBPE,Boltje TJ.Sialic acid O-acetylation: from biosynthesis to roles in health and disease.J Biol Chem2021;297:100906 PMCID:PMC8319020

[140] Kamerling JP.Identification of O-cetylated N-acylneuraminic acids by mass spectrometry.Carbohydr Res1975;41:7-17

[141] Mandal C,Vlasak R.Functions and biosynthesis of O-acetylated sialic acids.Top Curr Chem2015;366:1-30 PMCID:PMC7120186

[142] Surolia I,Chellappa V.Functionally defective germline variants of sialic acid acetylesterase in autoimmunity.Nature2010;466:243-7

[143] Arming S,Mayr J.The human Cas1 protein: a sialic acid-specific O-acetyltransferase?.Glycobiology2011;21:553-64 PMCID:PMC7108626

[144] Baumann AM,Buettner FF.9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate.Nat Commun2015;6:7673 PMCID:PMC4510713

[145] Arnesen T,Polevoda B.Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans.Proc Natl Acad Sci USA2009;106:8157-62 PMCID:PMC2688859

[146] Deng S.Protein N-terminal acetylation: structural basis, mechanism, versatility, and regulation.Trends Biochem Sci2021;46:15-27 PMCID:PMC7749037

[147] Aksnes H,Arnesen T.Co-translational, post-translational, and non-catalytic roles of N-terminal acetyltransferases.Mol Cell2019;73:1097-114 PMCID:PMC6962057

[148] Aksnes H,Marie M.First things first: vital protein marks by N-terminal acetyltransferases.Trends Biochem Sci2016;41:746-60

[149] Mullen JR,Moerschell RP.Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast.EMBO J1989;8:2067-75 PMCID:PMC401092

[150] Liszczak G,Foyn H,Arnesen T.Molecular basis for N-terminal acetylation by the heterodimeric NatA complex.Nat Struct Mol Biol2013;20:1098-105 PMCID:PMC3766382

[151] Deng S,Wei X,Petersson EJ.Structure and mechanism of acetylation by the N-terminal dual enzyme NatA/Naa50 complex.Structure2019;27:1057-70.e4 PMCID:PMC6610660

[152] Gottlieb L.Structure of human NatA and its regulation by the huntingtin interacting protein HYPK.Structure2018;26:925-935.e8 PMCID:PMC6031454

[153] Lentzsch AM,Gamerdinger M.NAC guides a ribosomal multienzyme complex for nascent protein processing.Nature2024;633:718-24

[154] Deng S,Gottlieb L,Marmorstein R.Molecular basis for N-terminal alpha-synuclein acetylation by human NatB.Elife2020;9e57491 PMCID:PMC7494357

[155] Vinueza-Gavilanes R,Larrea L.N-terminal acetylation mutants affect alpha-synuclein stability, protein levels and neuronal toxicity.Neurobiol Dis2020;137:104781

[156] Hong H,Zhang S,Wang H.Molecular basis of substrate specific acetylation by N-Terminal acetyltransferase NatB.Structure2017;25:641-9.e3

[157] Van Damme P,Jonckheere V.Expanded in vivo substrate profile of the yeast N-terminal acetyltransferase NatC.J Biol Chem2023;299:102824 PMCID:PMC9867985

[158] Van Damme P,Starheim KK.A role for human N-alpha acetyltransferase 30 (Naa30) in maintaining mitochondrial integrity.Mol Cell Proteomics2016;15:3361-72 PMCID:PMC5098035

[159] Deng S,Pan B.Molecular mechanism of N-terminal acetylation by the ternary NatC complex.Structure2021;29:1094-104.e4 PMCID:PMC8500922

[160] Grunwald S,Bock-Bierbaum T,Spahn CMT.Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates.Nat Commun2020;11:5506 PMCID:PMC7608589

[161] Magin RS,Marmorstein R.The molecular basis for histone H4- and H2A-specific amino-terminal acetylation by NatD.Structure2015;23:332-41 PMCID:PMC4318724

[162] Song OK,Waterborg JH.An Nalpha-acetyltransferase responsible for acetylation of the N-terminal residues of histones H4 and H2A.J Biol Chem2003;278:38109-12

[163] Deng S,Wei X,Marmorstein R.Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK.Nat Commun2020;11:818 PMCID:PMC7010799

[164] Damme P, Hole K, Gevaert K, Arnesen T. N-terminal acetylome analysis reveals the specificity of Naa50 (Nat5) and suggests a kinetic competition between N-terminal acetyltransferases and methionine aminopeptidases.Proteomics2015;15:2436-46

[165] Støve SI,Foyn H,Marmorstein R.Crystal structure of the golgi-associated human Nα-acetyltransferase 60 reveals the molecular determinants for substrate-specific acetylation.Structure2016;24:1044-56 PMCID:PMC4938767

[166] Aksnes H,Strømland Ø.Molecular determinants of the N-terminal acetyltransferase Naa60 anchoring to the Golgi membrane.J Biol Chem2017;292:6821-37 PMCID:PMC5399128

[167] Zegerman P,Kouzarides T.The putative tumour suppressor Fus-2 is an N-acetyltransferase.Oncogene2000;19:161-3

[168] Drazic A,Marie M.NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility.Proc Natl Acad Sci USA2018;115:4399-404 PMCID:PMC5924898

[169] Wiame E,Tyteca D.NAT6 acetylates the N-terminus of different forms of actin.FEBS J2018;285:3299-316

[170] Estruch R,Salas-Salvadó J.Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts.N Engl J Med2018;378:e34

[171] Nakamura M,Husain S.Glycogen synthase kinase-3α promotes fatty acid uptake and lipotoxic cardiomyopathy.Cell Metab2019;29:1119-34.e12 PMCID:PMC6677269

[172] Ahmad S,Lee IM.Mediterranean Diet adherence and risk of all-cause mortality in women.JAMA Netw Open2024;7:e2414322 PMCID:PMC11143458

[173] Ahmad S,Sun Q.Association of the mediterranean diet with onset of diabetes in the women's health study.JAMA Netw Open2020;3:e2025466 PMCID:PMC7677766

[174] Ahmad S,Demler OV.Assessment of risk factors and biomarkers associated with risk of cardiovascular disease among women consuming a mediterranean diet.JAMA Netw Open2018;1:e185708 PMCID:PMC6324327

[175] Alateeq K,Ambikairajah A.Association between dietary magnesium intake, inflammation, and neurodegeneration.Eur J Nutr2024;63:1807-18 PMCID:PMC11329609

[176] Tebar WR,Goulart AC.Combined association of novel and traditional inflammatory biomarkers with carotid artery plaque: GlycA versus C-reactive protein (ELSA-Brasil).Am J Cardiol2023;204:140-50

[177] Chiesa ST,Georgiopoulos G.Glycoprotein acetyls: a novel inflammatory biomarker of early cardiovascular risk in the young.J Am Heart Assoc2022;11:e024380 PMCID:PMC9245818

[178] Charidemou E,Ghirardi C.Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.EMBO J2024;43:1187-213 PMCID:PMC10987603

[179] Son SM,Breusegem SY,Rubinsztein DC.p300 nucleocytoplasmic shuttling underlies mTORC1 hyperactivation in Hutchinson-Gilford progeria syndrome.Nat Cell Biol2024;26:235-49 PMCID:PMC10866696

[180] Son SM,Stamatakou E,Menzies FM.Leucine regulates autophagy via acetylation of the mTORC1 component raptor.Nat Commun2020;11:3148 PMCID:PMC7305105

[181] Son SM,Lee H.Leucine signals to mTORC1 via its metabolite acetyl-coenzyme A.Cell Metab2019;29:192-201.e7 PMCID:PMC6331339

[182] Sabari BR,Allis CD.Metabolic regulation of gene expression through histone acylations.Nat Rev Mol Cell Biol2017;18:90-101 PMCID:PMC5320945

[183] Nakamura M.Gut microbiome: an effector of dietary nitrate that inhibits cardiometabolic disease?.Diabetes2023;72:835-7 PMCID:PMC10281812

[184] Lee JY,Bäumler AJ.The microbiome and gut homeostasis.Science2022;377:eabp9960

[185] Fellows R,Stellato C.Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.Nat Commun2018;9:105 PMCID:PMC5760624

[186] Gates LA,Lund PJ.Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression.Nat Metab2024;6:697-707 PMCID:PMC11520355

[187] Murashige D,Neinast M.Comprehensive quantification of fuel use by the failing and nonfailing human heart.Science2020;370:364-8 PMCID:PMC7871704

[188] Nakamura M.Mechanisms of physiological and pathological cardiac hypertrophy.Nat Rev Cardiol2018;15:387-407

[189] Zhang Y,Cochran JD.Mitochondrial pyruvate carriers are required for myocardial stress adaptation.Nat Metab2020;2:1248-64 PMCID:PMC8015649

[190] Fernandez-Caggiano M,Francois AA.Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy.Nat Metab2020;2:1223-31 PMCID:PMC7610404

[191] Seidelmann SB,Cheng S.Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis.Lancet Public Health2018;3:e419-28 PMCID:PMC6339822

[192] Newman JC,Zhao M.Ketogenic diet reduces midlife mortality and improves memory in aging mice.Cell Metab2017;26:547-57.e8 PMCID:PMC5605815

[193] Roberts MN,Tomilov AA.A ketogenic diet extends longevity and healthspan in adult mice.Cell Metab2018;27:1156 PMCID:PMC5957496

[194] Matsuura TR,Crawford PA.Ketones and the heart: metabolic principles and therapeutic implications.Circ Res2023;132:882-98 PMCID:PMC10289202

[195] Nakamura M.Ketone body can be a fuel substrate for failing heart.Cardiovasc Res2019;115:1567-9 PMCID:PMC6704386

[196] Nakamura M,Nakada Y.Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure.Cardiovasc Res2021;117:2365-76 PMCID:PMC8861266

[197] Schugar RC,André d’Avignon D,Kovacs A.Cardiomyocyte-specific deficiency of ketone body metabolism promotes accelerated pathological remodeling.Mol Metab2014;3:754-69 PMCID:PMC4209361

[198] Nielsen R,Gormsen LC.Cardiovascular effects of treatment with the ketone body 3-hydroxybutyrate in chronic heart failure patients.Circulation2019;139:2129-41 PMCID:PMC6493702

[199] Berg-Hansen K,Gopalasingam N.Beneficial effects of ketone ester in patients with cardiogenic shock: a randomized, controlled, double-blind trial.JACC Heart Fail2023;11:1337-47

[200] Shimazu T,Newman J.Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.Science2013;339:211-4 PMCID:PMC3735349

[201] Youm YH,Grant RW.The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease.Nat Med2015;21:263-9 PMCID:PMC4352123

[202] Han YM,Ding Y.β-Hydroxybutyrate prevents vascular senescence through hnRNP A1-mediated upregulation of Oct4.Mol Cell2018;71:1064-78.e5 PMCID:PMC6230553

[203] Horton JL,Lai L.Mitochondrial protein hyperacetylation in the failing heart.JCI Insight2016;2:e84897 PMCID:PMC4795836

[204] Walker MA,Villet O.Acetylation of muscle creatine kinase negatively impacts high-energy phosphotransfer in heart failure.JCI Insight2021;6:144301 PMCID:PMC7934860

[205] Deng Y,Li Q.Targeting mitochondria-inflammation circuit by β-hydroxybutyrate mitigates HFpEF.Circ Res2021;128:232-45

[206] Davidson MT,Lai L.Extreme acetylation of the cardiac mitochondrial proteome does not promote heart failure.Circ Res2020;127:1094-108 PMCID:PMC9161399

[207] Zhao Z,Xiang X.Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance.J Cell Biol2024;223:e202309090 PMCID:PMC11489267

[208] Wang Y,Ying L.Nicotinamide mononucleotide (NMN) Ameliorates free fatty acid-induced pancreatic β-cell dysfunction via the NAD⁺/AMPK/SIRT1/HIF-1α pathway.Int J Mol Sci2024;25:10534 PMCID:PMC11476918

[209] Black JC,Kitada T,Carey M.The SIRT2 deacetylase regulates autoacetylation of p300.Mol Cell2008;32:449-55 PMCID:PMC2645867

[210] Mariño G,Eisenberg T.Regulation of autophagy by cytosolic acetyl-coenzyme A.Mol Cell2014;53:710-25

[211] Lin SY,Liu Q.GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy.Science2012;336:477-81

[212] Cheng X,Zhu Q.Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of autophagosome maturation and lipid metabolism.Mol Cell2019;73:788-802.e7

[213] Sun T,Zhang P.Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth.Nat Commun2015;6:7215 PMCID:PMC4455096

[214] Huang R,Wan W.Deacetylation of nuclear LC3 drives autophagy initiation under starvation.Mol Cell2015;57:456-66

[215] Tham E,Santani A.Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features.Am J Hum Genet2015;96:507-13 PMCID:PMC4375419

[216] Zhang LX,Gonzaga-Jauregui C.Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants.Genet Med2020;22:1338-47 PMCID:PMC7737399

[217] Gaub A,Basilicata MF.Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation.Nat Commun2020;11:2243 PMCID:PMC7206058

[218] Li T,Yao C.Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with Koolen-de Vries syndrome in mice.Nat Commun2022;13:931 PMCID:PMC8854428

[219] Füllgrabe J,Heldring N.The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy.Nature2013;500:468-71 PMCID:PMC4006103

[220] Zehender A,Lin NY.TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy.Nat Commun2021;12:4404 PMCID:PMC8292318

[221] Mutlu B.GCN5 acetyltransferase in cellular energetic and metabolic processes.Biochim Biophys Acta Gene Regul Mech2021;1864:194626 PMCID:PMC7854474

[222] Volani C,Rainer J.GCN5 contributes to intracellular lipid accumulation in human primary cardiac stromal cells from patients affected by Arrhythmogenic cardiomyopathy.J Cell Mol Med2022;26:3687-701 PMCID:PMC9258704

[223] Ghosh AK.Acetyltransferase p300 is a putative epidrug target for amelioration of cellular aging-related cardiovascular disease.Cells2021;10:2839 PMCID:PMC8616404

[224] Homsy J,Shen Y.De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.Science2015;350:1262-6

[225] Jin SC,Zaidi S.Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.Nat Genet2017;49:1593-601 PMCID:PMC5675000

[226] Cheng H,Varland S.Truncating variants in NAA15 are associated with variable levels of intellectual disability, autism spectrum disorder, and congenital anomalies.Am J Hum Genet2018;102:985-94 PMCID:PMC5986698

[227] Cheng H,Marchi E.Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15.Hum Mol Genet2019;28:2900-19 PMCID:PMC6736318

[228] Ward T,Morton S.Mechanisms of congenital heart disease caused by NAA15 haploinsufficiency.Circ Res2021;128:1156-69 PMCID:PMC8048381

[229] Li D,Moonen JR.ALDH1A3 coordinates metabolism with gene regulation in pulmonary arterial hypertension.Circulation2021;143:2074-90 PMCID:PMC8289565

[230] Han Y,Reeps C.Histone acetylation and histone acetyltransferases show significant alterations in human abdominal aortic aneurysm.Clin Epigenetics2016;8:3 PMCID:PMC4711037

[231] Wen Y,Li Q.Spatiotemporal ATF3 expression determines VSMC fate in abdominal aortic aneurysm.Circ Res2024;134:1495-511

[232] Wang X,Lauth A.Conditional depletion of the acetyltransferase Tip60 protects against the damaging effects of myocardial infarction.J Mol Cell Cardiol2022;163:9-19 PMCID:PMC8816866

[233] Lei I,Gao W.Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation.Elife2021;10:e60311 PMCID:PMC8763402

[234] Huang C,Shao J.Aerobic training attenuates cardiac remodeling in mice post-myocardial infarction by inhibiting the p300/CBP-associated factor.FASEB J2024;38:e23780

[235] de Jong A,Peters EA.P300/CBP associated Factor (PCAF) deficiency enhances diet-induced atherosclerosis in ApoE3*Leiden mice via systemic inhibition of regulatory T cells.Front Cardiovasc Med2020;7:604821 PMCID:PMC7874080

[236] Liu S,Meng F.Microtubules sequester acetylated YAP in the cytoplasm and inhibit heart regeneration.Circulation2025;151:59-75 PMCID:PMC11671299

[237] Chen X,Liu Z,Martin JF.Knockout of SRC-1 and SRC-3 in mice decreases cardiomyocyte proliferation and causes a noncompaction cardiomyopathy phenotype.Int J Biol Sci2015;11:1056-72 PMCID:PMC4515817

[238] Suh JH,Nam D.Steroid receptor coactivator-2 (SRC-2) coordinates cardiomyocyte paracrine signaling to promote pressure overload-induced angiogenesis.J Biol Chem2017;292:21643-52 PMCID:PMC5766961

[239] Mullany LK,Leach JP.A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction.Proc Natl Acad Sci USA2020;117:31353-64 PMCID:PMC7733826

[240] McClendon LK,Panigrahi A.Transcriptional coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress.J Mol Cell Cardiol2024;194:70-84

[241] Chatterjee A,Lucci J.MOF acetyl transferase regulates transcription and respiration in mitochondria.Cell2016;167:722-738.e23

[242] Wang D,Chandel NS,Yi R.MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene promoters.Nat Commun2023;14:4404 PMCID:PMC10362062

[243] Guhathakurta S,Hoffmann JJ.COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function.Nat Metab2023;5:1931-52 PMCID:PMC10663164

[244] Hu Y,Liu C.Mitochondrial MOF regulates energy metabolism in heart failure via ATP5B hyperacetylation.Cell Rep2024;43:114839

[245] Baker DJ,Durik M.Naturally occurring p16^Ink4a-positive cells shorten healthy lifespan.Nature2016;530:184-9

[246] Schafer MJ,Kumar A.The senescence-associated secretome as an indicator of age and medical risk.JCI Insight2020;5:133668 PMCID:PMC7406245

[247] Sol J,Mota-Martorell N.Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome.Aging Cell2023;22:e13821 PMCID:PMC10265170

[248] Hamsanathan S,Prosser D.A molecular index for biological age identified from the metabolome and senescence-associated secretome in humans.Aging Cell2024;23:e14104 PMCID:PMC11019119

[249] Vermeij WP,Reiling E.Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.Nature2016;537:427-31

[250] Scheibye-Knudsen M,Fang EF.A high-fat diet and NAD⁺ activate Sirt1 to rescue premature aging in cockayne syndrome.Cell Metab2014;20:840-55 PMCID:PMC4261735

[251] Hamsanathan S,Han S.Integrated -omics approach reveals persistent DNA damage rewires lipid metabolism and histone hyperacetylation via MYS-1/Tip60.Sci Adv2022;8:eabl6083 PMCID:PMC8849393

[252] Perez-Campo FM,Lie-A-Ling M,Kouskoff V.MOZ-mediated repression of p16^INK4a is critical for the self-renewal of neural and hematopoietic stem cells.Stem Cells2014;32:1591-601

[253] Sheikh BN,El-Saafin F.MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway.Oncogene2015;34:5807-20

[254] Baell JB,Hermans SJ.Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth.Nature2018;560:253-7

[255] Mukohara T,Sommerhalder D.Inhibition of lysine acetyltransferase KAT6 in ER⁺HER2^- metastatic breast cancer: a phase 1 trial.Nat Med2024;30:2242-50 PMCID:PMC11333285

[256] Wang W,Sun S.A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence.Sci Transl Med2021;13:eabd2655

[257] Nagarajan P,Iyer CC,Arnold WD.Early-onset aging and mitochondrial defects associated with loss of histone acetyltransferase 1 (Hat1).Aging Cell2019;18:e12992 PMCID:PMC6718594

[258] Huang B,Zhu J.Inhibition of histone acetyltransferase GCN5 extends lifespan in both yeast and human cell lines.Aging Cell2020;19:e13129 PMCID:PMC7189995

[259] Sen P,Li CY.Histone Acetyltransferase p300 induces de novo super-enhancers to drive cellular senescence.Mol Cell2019;73:684-98.e8 PMCID:PMC6688479

[260] Wakita M,Sano O.A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells.Nat Commun2020;11:1935 PMCID:PMC7176673

[261] Serio S,Musolino E.Cardiac aging is promoted by pseudohypoxia increasing p300-induced glycolysis.Circ Res2023;133:687-703

[262] Foote K,Schmidt L.Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins.Cardiovasc Res2024;cvae091

[263] Li TY,Li H.The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress.Nat Aging2021;1:165-78 PMCID:PMC7116894

[264] Mayer A,Schwartz AL.Degradation of proteins with acetylated amino termini by the ubiquitin system.Science1989;244:1480-3

[265] Mueller F,Pathe C.Overlap of NatA and IAP substrates implicates N-terminal acetylation in protein stabilization.Sci Adv2021;7:eabc8590 PMCID:PMC7810383

[266] Guzman UH,Ree R.Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae.Nat Commun2023;14:4517 PMCID:PMC10374663

[267] Varland S,Kjosås I.N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.Nat Commun2023;14:6774 PMCID:PMC10611716