The histone acetylase PCAF is a nuclear receptor coactivator

Jorge C G Blanco, Saverio Minucci, Jianming Lu, Xiang Jiao Yang, Kristen K. Walker, Hongwu Chen, Ronald M. Evans, Yoshihiro Nakatani, Keiko Ozato

Research output: Contribution to journalArticle

326 Scopus citations

Abstract

Whereas the histone acetylase PCAF has been suggested to be part of a coactivator complex mediating transcriptional activation by the nuclear hormone receptors, the physical and functional interactions between nuclear receptors and PCAF have remained unclear. Our efforts to clarify these relationships have revealed two novel properties of nuclear receptors. First, we demonstrate that the RXR/RAR heterodimer directly recruits PCAF from mammalian cell extracts in a ligand-dependent manner and that increased expression of PCAF leads to enhanced retinoid-responsive transcription. Second, we demonstrate that, in vitro, PCAF directly associates with the DNA- binding domain of nuclear receptors, independently of p300/CBP binding, therefore defining a novel cofactor interaction surface. Furthermore, our results show that dissociation of corepressors enables ligand-dependent PCAF binding to the receptors. This observation illuminates how a ligand- dependent receptor function can be propagated to regions outside the ligand- binding domain itself. On the basis of these observations, we suggest that PCAF may play a more central role in nuclear receptor function than previously anticipated.

Original languageEnglish (US)
Pages (from-to)1638-1651
Number of pages14
JournalGenes and Development
Volume12
Issue number11
StatePublished - Jun 1 1998
Externally publishedYes

Keywords

  • Histone acetylation
  • ILAR
  • PCAF
  • Retinoids
  • RXR
  • Steroid receptors

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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