The SIRT2 Deacetylase Regulates Autoacetylation of p300

Joshua C. Black, Amber Mosley, Tasuku Kitada, Michael Washburn, Michael Carey

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)449-455
Number of pages7
JournalMolecular Cell
Volume32
Issue number3
DOIs
StatePublished - Nov 7 2008
Externally publishedYes

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Histone Acetyltransferases
Histone Deacetylases
Acetylation
RNA Interference
NAD
Lysine
Chromatin
Catalytic Domain
Genes
p300-CBP-associated factor

Keywords

  • PROTEINS
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The SIRT2 Deacetylase Regulates Autoacetylation of p300. / Black, Joshua C.; Mosley, Amber; Kitada, Tasuku; Washburn, Michael; Carey, Michael.

In: Molecular Cell, Vol. 32, No. 3, 07.11.2008, p. 449-455.

Research output: Contribution to journalArticle

Black, JC, Mosley, A, Kitada, T, Washburn, M & Carey, M 2008, 'The SIRT2 Deacetylase Regulates Autoacetylation of p300', Molecular Cell, vol. 32, no. 3, pp. 449-455. https://doi.org/10.1016/j.molcel.2008.09.018
Black, Joshua C. ; Mosley, Amber ; Kitada, Tasuku ; Washburn, Michael ; Carey, Michael. / The SIRT2 Deacetylase Regulates Autoacetylation of p300. In: Molecular Cell. 2008 ; Vol. 32, No. 3. pp. 449-455.
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