Antiestrogen can establish nonproductive receptor complexes and alter chromatin structure at target enhancers

Tony A. Pham, Jonathan F. Elliston, Zafar Nawaz, Donald P. Mcdonnell, Ming Jer Tsai, Bert W. O'Malley

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

We describe in this report experiments in vivo that demonstrate that antiestrogens promote DNA binding of the estrogen receptor without efficiently inducing transcription. When the receptor is modified to carry a foreign unregulated transactivation domain, transcription can be induced efficiently by both estrogen and antiestrogens. Under apparent saturation conditions, antihonnone-receptor complexes binding to responsive enhancer elements elicit only a low level of transcription. In addition, we show that both estrogen and an antiestrogen, nafoxidine, effect very similar alterations in chromatin structure at a responsive promoter. These results indicate that in vivo steroid receptor action can be regulated subsequent to the DNA binding step, by regulating interactions with the target transcriptional machinery. In this regard, antihormones can function by establishing receptor-DNA complexes that are transcriptionally nonproductive.

Original languageEnglish
Pages (from-to)3125-3129
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number8
StatePublished - Dec 1 1991
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Chromatin
Nafoxidine
Estrogens
Steroid Receptors
DNA
Estrogen Receptors
Transcriptional Activation

Keywords

  • DNA binding
  • Estrogen receptor
  • Transactivation

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Antiestrogen can establish nonproductive receptor complexes and alter chromatin structure at target enhancers. / Pham, Tony A.; Elliston, Jonathan F.; Nawaz, Zafar; Mcdonnell, Donald P.; Tsai, Ming Jer; O'Malley, Bert W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 8, 01.12.1991, p. 3125-3129.

Research output: Contribution to journalArticle

Pham, Tony A. ; Elliston, Jonathan F. ; Nawaz, Zafar ; Mcdonnell, Donald P. ; Tsai, Ming Jer ; O'Malley, Bert W. / Antiestrogen can establish nonproductive receptor complexes and alter chromatin structure at target enhancers. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 8. pp. 3125-3129.
@article{45af1240e4a24bcc927044d5a6e5372b,
title = "Antiestrogen can establish nonproductive receptor complexes and alter chromatin structure at target enhancers",
abstract = "We describe in this report experiments in vivo that demonstrate that antiestrogens promote DNA binding of the estrogen receptor without efficiently inducing transcription. When the receptor is modified to carry a foreign unregulated transactivation domain, transcription can be induced efficiently by both estrogen and antiestrogens. Under apparent saturation conditions, antihonnone-receptor complexes binding to responsive enhancer elements elicit only a low level of transcription. In addition, we show that both estrogen and an antiestrogen, nafoxidine, effect very similar alterations in chromatin structure at a responsive promoter. These results indicate that in vivo steroid receptor action can be regulated subsequent to the DNA binding step, by regulating interactions with the target transcriptional machinery. In this regard, antihormones can function by establishing receptor-DNA complexes that are transcriptionally nonproductive.",
keywords = "DNA binding, Estrogen receptor, Transactivation",
author = "Pham, {Tony A.} and Elliston, {Jonathan F.} and Zafar Nawaz and Mcdonnell, {Donald P.} and Tsai, {Ming Jer} and O'Malley, {Bert W.}",
year = "1991",
month = "12",
day = "1",
language = "English",
volume = "88",
pages = "3125--3129",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Antiestrogen can establish nonproductive receptor complexes and alter chromatin structure at target enhancers

AU - Pham, Tony A.

AU - Elliston, Jonathan F.

AU - Nawaz, Zafar

AU - Mcdonnell, Donald P.

AU - Tsai, Ming Jer

AU - O'Malley, Bert W.

PY - 1991/12/1

Y1 - 1991/12/1

N2 - We describe in this report experiments in vivo that demonstrate that antiestrogens promote DNA binding of the estrogen receptor without efficiently inducing transcription. When the receptor is modified to carry a foreign unregulated transactivation domain, transcription can be induced efficiently by both estrogen and antiestrogens. Under apparent saturation conditions, antihonnone-receptor complexes binding to responsive enhancer elements elicit only a low level of transcription. In addition, we show that both estrogen and an antiestrogen, nafoxidine, effect very similar alterations in chromatin structure at a responsive promoter. These results indicate that in vivo steroid receptor action can be regulated subsequent to the DNA binding step, by regulating interactions with the target transcriptional machinery. In this regard, antihormones can function by establishing receptor-DNA complexes that are transcriptionally nonproductive.

AB - We describe in this report experiments in vivo that demonstrate that antiestrogens promote DNA binding of the estrogen receptor without efficiently inducing transcription. When the receptor is modified to carry a foreign unregulated transactivation domain, transcription can be induced efficiently by both estrogen and antiestrogens. Under apparent saturation conditions, antihonnone-receptor complexes binding to responsive enhancer elements elicit only a low level of transcription. In addition, we show that both estrogen and an antiestrogen, nafoxidine, effect very similar alterations in chromatin structure at a responsive promoter. These results indicate that in vivo steroid receptor action can be regulated subsequent to the DNA binding step, by regulating interactions with the target transcriptional machinery. In this regard, antihormones can function by establishing receptor-DNA complexes that are transcriptionally nonproductive.

KW - DNA binding

KW - Estrogen receptor

KW - Transactivation

UR - http://www.scopus.com/inward/record.url?scp=0026341234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026341234&partnerID=8YFLogxK

M3 - Article

VL - 88

SP - 3125

EP - 3129

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -