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

T. A. Pham, J. F. Elliston, Z. Nawaz, D. P. McDonnell, M. J. Tsai, B. W. O'Malley

Research output: Contribution to journalArticle

93 Scopus citations

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

Keywords

  • DNA binding
  • Estrogen receptor
  • Transactivation

ASJC Scopus subject areas

  • General
  • Genetics

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