Histone acetyltransferase p300

Definition:

Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1 or SIRT2. Acetylates 'Lys-131' of ALX1 and acts as its coactivator. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of p53/TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis. Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acetylates 'Lys-247' of EGR2 (By similarity). Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity. Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity. Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter. Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity. Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Acetylates MEF2D. Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degradation, this mechanism may be involved in CD4/CD8 lineage differentiation. Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity). Acetylates PCK1 and promotes PCK1 anaplerotic activity. Acetylates RXRA and RXRG. Acetylates isoform M2 of PKM (PKM2), promoting its homodimerization and conversion into a protein kinase. In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation or propionylation, respectively. Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low. Also acts as a histone butyryltransferase; butyrylation marks active promoters. Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription. Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes. Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway.; (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein.

References:

[1]. Danmei Xu, et al. A transcription cofactor required for the heat-shock response. EMBO Rep. 2008 Jul;9(7):662-9. [Content Brief]

[2]. W Xu, et al. A transcriptional switch mediated by cofactor methylation. Science. 2001 Dec 21;294(5551):2507-11. [Content Brief]

[3]. Joshua C Black, et al. The SIRT2 deacetylase regulates autoacetylation of p300. Mol Cell. 2008 Nov 7;32(3):449-55. [Content Brief]

[4]. Di Zhang, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019 Oct;574(7779):575-580. [Content Brief]

[5]. R E Kiernan, et al. HIV-1 tat transcriptional activity is regulated by acetylation. EMBO J. 1999 Nov 1;18(21):6106-18. [Content Brief]

[6]. Min Zhang, et al. p300-mediated acetylation stabilizes the Th-inducing POK factor. J Immunol. 2010 Oct 1;185(7):3960-9. [Content Brief]

[7]. C Demonacos, et al. A TPR motif cofactor contributes to p300 activity in the p53 response. Mol Cell. 2001 Jul;8(1):71-84. [Content Brief]

[8]. Oksana R Bereshchenko, et al. Acetylation inactivates the transcriptional repressor BCL6. Nat Genet. 2002 Dec;32(4):606-13. [Content Brief]

[9]. He Huang, et al. p300-Mediated Lysine 2-Hydroxyisobutyrylation Regulates Glycolysis. Mol Cell. 2018 May 17;70(4):663-678.e6. [Content Brief]

[10]. Claudia C S Chini, et al. HDAC3 is negatively regulated by the nuclear protein DBC1. J Biol Chem. 2010 Dec 24;285(52):40830-7. [Content Brief]

[11]. V V Ogryzko, et al. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996 Nov 29;87(5):953-9. [Content Brief]

[12]. Constantinos Demonacos, et al. A new effector pathway links ATM kinase with the DNA damage response. Nat Cell Biol. 2004 Oct;6(10):968-76. [Content Brief]

[13]. Younho Han, et al. Acetylation of Sirt2 by p300 attenuates its deacetylase activity. Biochem Biophys Res Commun. 2008 Oct 31;375(4):576-80. [Content Brief]

[14]. Anne M Curtis, et al. Histone acetyltransferase-dependent chromatin remodeling and the vascular clock. J Biol Chem. 2004 Feb 20;279(8):7091-7. [Content Brief]

[15]. Woojin An, et al. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell. 2004 Jun 11;117(6):735-48. [Content Brief]

[16]. Feng-Ming Wang, et al. Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation. Biochem J. 2011 Jan 1;433(1):245-52. [Content Brief]

[17]. Wen-Xiu Zhao, et al. Orphan receptor TR3 attenuates the p300-induced acetylation of retinoid X receptor-alpha. Mol Endocrinol. 2007 Dec;21(12):2877-89. [Content Brief]

[18]. Yi Qiu, et al. HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription. Mol Cell. 2006 Jun 9;22(5):669-79. [Content Brief]

[19]. Anupama E Gururaj, et al. MTA1, a transcriptional activator of breast cancer amplified sequence 3. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6670-5. [Content Brief]

[20]. Yue Chen, et al. Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics. 2007 May;6(5):812-9. [Content Brief]

[21]. Yutao Yang, et al. Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses. Biochim Biophys Acta. 2015 Mar;1849(3):270-81. [Content Brief]

[22]. S Hasan, et al. Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300. Mol Cell. 2001 Jun;7(6):1221-31. [Content Brief]

[23]. A W Snowden, et al. A novel transcriptional repression domain mediates p21(WAF1/CIP1) induction of p300 transactivation. Mol Cell Biol. 2000 Apr;20(8):2676-86. [Content Brief]

[24]. Benjamin R Sabari, et al. Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. Mol Cell. 2015 Apr 16;58(2):203-15. [Content Brief]

[25]. Ornella Cazzalini, et al. CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis. Nucleic Acids Res. 2014 Jul;42(13):8433-48. [Content Brief]

[26]. Philipp Tropberger, et al. Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer. Cell. 2013 Feb 14;152(4):859-72. [Content Brief]

[27]. Manuela Delvecchio, et al. Structure of the p300 catalytic core and implications for chromatin targeting and HAT regulation. Nat Struct Mol Biol. 2013 Sep;20(9):1040-6. [Content Brief]

[28]. Lei Lv, et al. Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization. Mol Cell. 2013 Nov 7;52(3):340-52. [Content Brief]

[29]. José Bragança, et al. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. J Biol Chem. 2003 May 2;278(18):16021-9. [Content Brief]

[30]. L Deng, et al. Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones. Virology. 2000 Nov 25;277(2):278-95. [Content Brief]

[31]. Valérie Perrot, et al. The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. Mol Endocrinol. 2005 Sep;19(9):2283-98. [Content Brief]

[32]. Katerina Hatzi, et al. A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters. Cell Rep. 2013 Aug 15;4(3):578-88. [Content Brief]

[33]. Pedro Latorre-Muro, et al. Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions. Mol Cell. 2018 Sep 6;71(5):718-732.e9. [Content Brief]

[34]. Takashi Iioka, et al. P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain. J Bone Miner Res. 2003 Aug;18(8):1419-29. [Content Brief]

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