Regulation of the p300 HAT domain via a novel activation loop

Paul R. Thompson, Dongxia Wang, Ling Wang, Marcella Fulco, Natalia Pediconi, Dianzheng Zhang, Woojin An, Qingyuan Ge, Robert G. Roeder, Jiemin Wong, Massimo Levrero, Vittorio Sartorelli, Robert J. Cotter, Philip A. Cole

Research output: Contribution to journalArticlepeer-review


The transcriptional coactivator p300 is a histone acetyltransferase (HAT) whose function is critical for regulating gene expression in mammalian cells. However, the molecular events that regulate p300 HAT activity are poorly understood. We evaluated autoacetylation of the p300 HAT protein domain to determine its function. Using expressed protein ligation, the p300 HAT protein domain was generated in hypoacetylated form and found to have reduced catalytic activity. This basal catalytic rate was stimulated by autoacetylation of several key lysine sites within an apparent activation loop motif. This post-translational modification and catalytic regulation of p300 HAT activity is conceptually analogous to the activation of most protein kinases by autophosphorylation. We therefore propose that this autoregulatory loop could influence the impact of p300 on a wide variety of signaling and transcriptional events.

Original languageEnglish (US)
Pages (from-to)308-315
Number of pages8
JournalNature Structural and Molecular Biology
Issue number4
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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