title: The SIRT2 deacetylase regulates autoacetylation of p300.
abstract: Autoacetylation of the p300 histone acetyltransferase controls the transition between VP16-mediated chromatin acetylation and preinitiation complex (PIC) assembly. Currently, it is unknown if and how autoacetylated p300 is deacetylated. We found that the NAD(+)-dependent histone deacetylase SIRT2 deacetylates p300 in vitro and in cells. SIRT2 deacetylates lysine residues in the catalytic domain of p300 and restores binding of p300 to the PIC. RNAi-mediated depletion or chemical inhibition of SIRT2 in cells results in accumulation of acetylated p300. The altered ac-p300/p300 ratio in SIRT2-depleted cells results in decreased p300 recruitment to an integrated VP16-responsive gene and inhibition of transcription. We conclude that p300 undergoes a dynamic cycle of autoacetylation and deacetylation.
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, BSRB 351A, 615 Charles E. Young Drive South, Los Angeles, CA 90095-1737, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Black
authors.forename: Amber
authors.initials: A
authors.lastname: Mosley
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kitada
authors.forename: Michael
authors.initials: M
authors.lastname: Washburn
authors.forename: Michael
authors.initials: M
authors.lastname: Carey
mesh_terms: D000107:Acetylation; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D011994:Recombinant Proteins; D056565:Sirtuin 2; D037761:Sirtuins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C474199:SIRT2 protein, human