BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation

Mol Cell Biol. 2000 Oct;20(20):7541-9. doi: 10.1128/MCB.20.20.7541-7549.2000.

Abstract

Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER-BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation / drug effects
  • CREB-Binding Protein
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA Helicases
  • DNA-Binding Proteins / metabolism
  • Estrogens / pharmacology*
  • Histone Acetyltransferases
  • Histone Deacetylases / metabolism
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Ligands
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Coactivator 1
  • Promoter Regions, Genetic / genetics*
  • Protein Binding / drug effects
  • Receptors, Estrogen / metabolism*
  • Response Elements / genetics*
  • Signal Transduction / drug effects
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • Transcriptional Activation / drug effects
  • Tumor Cells, Cultured

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Estrogens
  • Histones
  • Hydroxamic Acids
  • Ligands
  • Nuclear Proteins
  • Receptors, Estrogen
  • Trans-Activators
  • Transcription Factors
  • trichostatin A
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1
  • Histone Deacetylases
  • SMARCA4 protein, human
  • DNA Helicases