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Negative Regulation by Glucocorticoids Through Interference with a cAMP Responsive Enhancer

Science
15 Jul 1988
Vol 241, Issue 4863
pp. 350-353

Abstract

Although steroid hormone receptors are known to activate gene expression by binding to specific hormone-dependent enhancers, the mechanisms by which steroids inhibit the transcription of specific genes are unknown. It is shown here by gene transfer studies that the same glucocorticoid receptor that activates gene expression can negatively regulate expression of the human glycoprotein hormone α-subunit gene. Glucocorticoid inhibition was conferred by a 52-nucleotide region that also contains elements crucial both for adenosine 3′,5′-monophosphate (cAMP) responsiveness and for placental-specific expression of this gene and was observed only under conditions in which these elements were functioning as enhancers. Purified glucocorticoid receptor was found to bind to DNA that overlap the cAMP responsive elements sites in this region. It is hypothesized that steroid receptors negatively regulate gene expression by interfering with the activity or binding of other important transcription factors.

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Published In

Science
Volume 241 | Issue 4863
15 July 1988

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Published in print: 15 July 1988

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Ingrid E. Akerblom
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.
Department of Biology, University of California, San Diego, CA 92093.
Emily P. Slater
Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 1, D-3550 Marburg, FRG.
Miguel Beato
Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 1, D-3550 Marburg, FRG.
John D. Baxter
Metabolic Research Unit, Departments of Medicine and Biochemistry/Biophysics, University of California, San Francisco, CA 94143.
Pamela L. Mellon
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.

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