Abstract

The regulation of gene expression by nuclear receptors controls the phenotypic properties and diverse biologies of target cells. In breast cancer cells, estrogen receptor alpha (ERα) is a master regulator of transcriptional stimulation and repression, yet the mechanisms by which agonist-bound ERα elicits repression are poorly understood. We analyzed early estrogen-repressed genes and found that ERα is recruited to ERα binding sites of these genes, albeit more transiently and less efficiently than for estrogen-stimulated genes. Of multiple cofactors studied, only p300 was recruited to ERα binding sites of repressed genes, and its knockdown prevented estrogen-mediated gene repression. Because p300 is involved in transcription initiation, we tested whether ERα might be trying to stimulate transcription at repressed genes, with ultimately failure and a shift to a repressive program. We found that estrogen increases transcription in a rapid but transient manner at early estrogen-repressed genes but that this is followed by recruitment of the corepressor CtBP1, a p300-interacting partner that plays an essential role in the repressive process. Thus, at early estrogen-repressed genes, ERα initiates transient stimulation of transcription but fails to maintain the transcriptional process observed at estrogen-stimulated genes; rather, it uses p300 to recruit CtBP1-containing complexes, eliciting chromatin modifications that lead to transcriptional repression.

Original languageEnglish (US)
Pages (from-to)1749-1759
Number of pages11
JournalMolecular and cellular biology
Volume29
Issue number7
DOIs
StatePublished - Apr 1 2009

Fingerprint

Genetic Transcription
Estrogen Receptor alpha
Estrogens
Genes
Binding Sites
Gene Knockdown Techniques
Co-Repressor Proteins
Gene Expression Regulation
Cytoplasmic and Nuclear Receptors
Chromatin
Cell Biology
Breast Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Estrogen receptor alpha represses transcription of early target genes via p300 and CtBP1. / Stossi, Fabio; Madak-Erdogan, Zeynep; Katzenellenbogen, Benita S.

In: Molecular and cellular biology, Vol. 29, No. 7, 01.04.2009, p. 1749-1759.

Research output: Contribution to journalArticle

@article{d87ff1f48c3e4ccf94bc1cda0e9a7495,
title = "Estrogen receptor alpha represses transcription of early target genes via p300 and CtBP1",
abstract = "The regulation of gene expression by nuclear receptors controls the phenotypic properties and diverse biologies of target cells. In breast cancer cells, estrogen receptor alpha (ERα) is a master regulator of transcriptional stimulation and repression, yet the mechanisms by which agonist-bound ERα elicits repression are poorly understood. We analyzed early estrogen-repressed genes and found that ERα is recruited to ERα binding sites of these genes, albeit more transiently and less efficiently than for estrogen-stimulated genes. Of multiple cofactors studied, only p300 was recruited to ERα binding sites of repressed genes, and its knockdown prevented estrogen-mediated gene repression. Because p300 is involved in transcription initiation, we tested whether ERα might be trying to stimulate transcription at repressed genes, with ultimately failure and a shift to a repressive program. We found that estrogen increases transcription in a rapid but transient manner at early estrogen-repressed genes but that this is followed by recruitment of the corepressor CtBP1, a p300-interacting partner that plays an essential role in the repressive process. Thus, at early estrogen-repressed genes, ERα initiates transient stimulation of transcription but fails to maintain the transcriptional process observed at estrogen-stimulated genes; rather, it uses p300 to recruit CtBP1-containing complexes, eliciting chromatin modifications that lead to transcriptional repression.",
author = "Fabio Stossi and Zeynep Madak-Erdogan and Katzenellenbogen, {Benita S.}",
year = "2009",
month = "4",
day = "1",
doi = "10.1128/MCB.01476-08",
language = "English (US)",
volume = "29",
pages = "1749--1759",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Estrogen receptor alpha represses transcription of early target genes via p300 and CtBP1

AU - Stossi, Fabio

AU - Madak-Erdogan, Zeynep

AU - Katzenellenbogen, Benita S.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - The regulation of gene expression by nuclear receptors controls the phenotypic properties and diverse biologies of target cells. In breast cancer cells, estrogen receptor alpha (ERα) is a master regulator of transcriptional stimulation and repression, yet the mechanisms by which agonist-bound ERα elicits repression are poorly understood. We analyzed early estrogen-repressed genes and found that ERα is recruited to ERα binding sites of these genes, albeit more transiently and less efficiently than for estrogen-stimulated genes. Of multiple cofactors studied, only p300 was recruited to ERα binding sites of repressed genes, and its knockdown prevented estrogen-mediated gene repression. Because p300 is involved in transcription initiation, we tested whether ERα might be trying to stimulate transcription at repressed genes, with ultimately failure and a shift to a repressive program. We found that estrogen increases transcription in a rapid but transient manner at early estrogen-repressed genes but that this is followed by recruitment of the corepressor CtBP1, a p300-interacting partner that plays an essential role in the repressive process. Thus, at early estrogen-repressed genes, ERα initiates transient stimulation of transcription but fails to maintain the transcriptional process observed at estrogen-stimulated genes; rather, it uses p300 to recruit CtBP1-containing complexes, eliciting chromatin modifications that lead to transcriptional repression.

AB - The regulation of gene expression by nuclear receptors controls the phenotypic properties and diverse biologies of target cells. In breast cancer cells, estrogen receptor alpha (ERα) is a master regulator of transcriptional stimulation and repression, yet the mechanisms by which agonist-bound ERα elicits repression are poorly understood. We analyzed early estrogen-repressed genes and found that ERα is recruited to ERα binding sites of these genes, albeit more transiently and less efficiently than for estrogen-stimulated genes. Of multiple cofactors studied, only p300 was recruited to ERα binding sites of repressed genes, and its knockdown prevented estrogen-mediated gene repression. Because p300 is involved in transcription initiation, we tested whether ERα might be trying to stimulate transcription at repressed genes, with ultimately failure and a shift to a repressive program. We found that estrogen increases transcription in a rapid but transient manner at early estrogen-repressed genes but that this is followed by recruitment of the corepressor CtBP1, a p300-interacting partner that plays an essential role in the repressive process. Thus, at early estrogen-repressed genes, ERα initiates transient stimulation of transcription but fails to maintain the transcriptional process observed at estrogen-stimulated genes; rather, it uses p300 to recruit CtBP1-containing complexes, eliciting chromatin modifications that lead to transcriptional repression.

UR - http://www.scopus.com/inward/record.url?scp=63049112988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63049112988&partnerID=8YFLogxK

U2 - 10.1128/MCB.01476-08

DO - 10.1128/MCB.01476-08

M3 - Article

C2 - 19188451

AN - SCOPUS:63049112988

VL - 29

SP - 1749

EP - 1759

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -