Transcription factor interactions: Selectors of positive or negative regulation from a single DNA element

Marc I. Diamond, Jeffrey N. Miner, Steven K. Yoshinaga, Keith R. Yamamoto

Research output: Contribution to journalArticle

1035 Scopus citations

Abstract

The mechanism by which a single factor evokes opposite regulatory effects from a specific DNA sequence is not well understood. In this study, a 25-base pair element that resides upstream of the mouse proliferin gene was examined; it conferred on linked promoters either positive or negative glucocorticoid regulation, depending upon physiological context. This sequence, denoted a "composite" glucocorticoid response element (GRE), was bound selectively in vitro both by the glucocorticoid receptor and by c-Jun and c-Fos, components of the phorbol ester-activated AP-1 transcription factor. Indeed, c-Jun and c-Fos served as selectors of hormone responsiveness: the composite GRE was inactive in the absence of c-Jun, whereas it conferred a positive glucocorticoid effect in the presence of c-Jun, and a negative glucocorticoid effect in the presence of c-Jun and relatively high levels of c-Fos. The receptor also interacted selectively with c-Jun in vitro. A general model for composite GRE action is proposed that invokes both DNA binding and protein-protein interactions by receptor and nonreceptor factors.

Original languageEnglish (US)
Pages (from-to)1266-1272
Number of pages7
JournalScience
Volume249
Issue number4974
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • General

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