The SIRT2 deacetylase regulates autoacetylation of p300.
Black JC, Mosley A, Kitada T, Washburn M, Carey M.
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.
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.
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PMID: 18995842 [PubMed - indexed for MEDLINE]