Mechanism of synergistic transcriptional transactivation by the human glucocorticoid receptor

A. P.H. Wright, J. A. Gustafsson

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Induction of transcription from a promoter with two upstream glucocorticoid response elements is 10- to 20-fold greater than that from a similar promoter with only one response element. We have shown that interactions involving the major transactivation domain of the glucocorticoid receptor (τ1) are the sole determinant of such synergistic transactivation by the receptor. The other transactivation domain of the receptor (τ2) did not mediate synergistic transactivation, and therefore the ability to synergize is operationally distinct from the transactivation function per se. The level of synergistic transactivation observed in vivo can be accounted for by the level of cooperative DNA binding seen in vitro for a glucocorticoid receptor derivative containing only the τ1 and DNA-binding domains. Cooperative DNA binding was also observed using a τ1-DNA-binding domain protein, which was expressed in Escherichia coli and extensively purified. Therefore, it is likely that direct protein-protein interactions between τ1 domains mediate the cooperative DNA binding. The role of cooperative DNA binding for synergistic transactivation in vivo is discussed in relation to other possible mechanisms.

Original languageEnglish (US)
Pages (from-to)8283-8287
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number19
DOIs
StatePublished - 1991

Keywords

  • Cooperative DNA binding
  • Steroid hormone action
  • Yeast

ASJC Scopus subject areas

  • General
  • Genetics

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