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Science 15 July 1988:
Vol. 241. no. 4863, pp. 350 - 353
DOI: 10.1126/science.2838908
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Articles

Science, Vol 241, Issue 4863, 350-353
Copyright © 1988 by American Association for the Advancement of Science

articles

Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer

IE Akerblom, EP Slater, M Beato, JD Baxter, and PL Mellon

Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.

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 alpha-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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Glucocorticoid-mediated repression of nuclear factor-kappa Bdependent transcription involves direct interference with transactivation.
K. De Bosscher, M. L. Schmitz, W. Vanden Berghe, S. Plaisance, W. Fiers, and G. Haegeman (1997)
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The basic region of AP-1 specifies glucocorticoid receptor activity at a composite response element..
J N Miner and K R Yamamoto (1992)
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Modulation of the IgH enhancer's cell type specificity through a genetic switch..
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Transcription factor interactions: selectors of positive or negative regulation from a single DNA element.
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Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins.
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Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression..
J C Mordacq and D I Linzer (1989)
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Science. ISSN 0036-8075 (print), 1095-9203 (online)