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

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
Pages (from-to)1638-1651
Number of pages14
JournalGenes and Development
Volume12
Issue number11
Publication statusPublished - Jun 1 1998

Fingerprint

Nuclear Receptor Coactivators
Cytoplasmic and Nuclear Receptors
Ligands
Co-Repressor Proteins
Retinoids
Cell Extracts
Transcriptional Activation
p300-CBP-associated factor
DNA

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Blanco, J. C. G., Minucci, S., Lu, J., Yang, X. J., Walker, K. K., Chen, H., ... Ozato, K. (1998). The histone acetylase PCAF is a nuclear receptor coactivator. Genes and Development, 12(11), 1638-1651.

The histone acetylase PCAF is a nuclear receptor coactivator. / Blanco, Jorge C G; Minucci, Saverio; Lu, Jianming; Yang, Xiang Jiao; Walker, Kristen K.; Chen, Hongwu; Evans, Ronald M.; Nakatani, Yoshihiro; Ozato, Keiko.

In: Genes and Development, Vol. 12, No. 11, 01.06.1998, p. 1638-1651.

Research output: Contribution to journalArticle

Blanco, JCG, Minucci, S, Lu, J, Yang, XJ, Walker, KK, Chen, H, Evans, RM, Nakatani, Y & Ozato, K 1998, 'The histone acetylase PCAF is a nuclear receptor coactivator', Genes and Development, vol. 12, no. 11, pp. 1638-1651.
Blanco JCG, Minucci S, Lu J, Yang XJ, Walker KK, Chen H et al. The histone acetylase PCAF is a nuclear receptor coactivator. Genes and Development. 1998 Jun 1;12(11):1638-1651.
Blanco, Jorge C G ; Minucci, Saverio ; Lu, Jianming ; Yang, Xiang Jiao ; Walker, Kristen K. ; Chen, Hongwu ; Evans, Ronald M. ; Nakatani, Yoshihiro ; Ozato, Keiko. / The histone acetylase PCAF is a nuclear receptor coactivator. In: Genes and Development. 1998 ; Vol. 12, No. 11. pp. 1638-1651.
@article{05077ca63fea4c128f093170639ff97f,
title = "The histone acetylase PCAF is a nuclear receptor coactivator",
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.",
keywords = "Histone acetylation, ILAR, PCAF, Retinoids, RXR, Steroid receptors",
author = "Blanco, {Jorge C G} and Saverio Minucci and Jianming Lu and Yang, {Xiang Jiao} and Walker, {Kristen K.} and Hongwu Chen and Evans, {Ronald M.} and Yoshihiro Nakatani and Keiko Ozato",
year = "1998",
month = "6",
day = "1",
language = "English",
volume = "12",
pages = "1638--1651",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "11",

}

TY - JOUR

T1 - The histone acetylase PCAF is a nuclear receptor coactivator

AU - Blanco, Jorge C G

AU - Minucci, Saverio

AU - Lu, Jianming

AU - Yang, Xiang Jiao

AU - Walker, Kristen K.

AU - Chen, Hongwu

AU - Evans, Ronald M.

AU - Nakatani, Yoshihiro

AU - Ozato, Keiko

PY - 1998/6/1

Y1 - 1998/6/1

N2 - 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.

AB - 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.

KW - Histone acetylation

KW - ILAR

KW - PCAF

KW - Retinoids

KW - RXR

KW - Steroid receptors

UR - http://www.scopus.com/inward/record.url?scp=2642662483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642662483&partnerID=8YFLogxK

M3 - Article

C2 - 9620851

AN - SCOPUS:2642662483

VL - 12

SP - 1638

EP - 1651

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 11

ER -