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Volume 271, Number 34, Issue of August 23, 1996 pp. 20412-20420
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Glucocorticoid Repression of the Mouse Gonadotropin-releasing Hormone Gene Is Mediated by Promoter Elements That Are Recognized by Heteromeric Complexes Containing Glucocorticoid Receptor

(Received for publication, February 22, 1996, and in revised form, May 6, 1996)

Uma R. Chandran Dagger , Barbara Attardi § , Robert Friedman § , Zhou-wen Zheng , James L. Roberts and Donald B. DeFranco Dagger

From the Dagger  Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, the § Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and the  Arthur M. Fishberg Research Center for Neurobiology, Mt. Sinai School of Medicine, New York, New York 10029

We have identified two regions of the mouse gonadotropin-releasing hormone (GnRH) promoter, one between -237 and -201 (distal element) and the other between -184 and -150 (proximal element), which are required for glucocorticoid repression in transiently transfected GT1-7 cells. These sequences show no similarity to known positive or negative glucocorticoid response elements (nGREs) and do not function when placed upstream of heterologous viral promoters. The glucocorticoid receptor (GR) does not bind directly to the distal or proximal promoter elements but may participate in glucocorticoid repression of GnRH gene transcription by virtue of its association within multiprotein complexes at these nGREs. Electrophoretic mobility shift assays with GT1-7 nuclear extract demonstrate the presence of GR-containing protein complexes on GnRH nGREs. One protein that co-occupies the distal nGRE in vitro along with GR is the POU domain transcription factor Oct-1. Thus, the tethering of GR to the GnRH distal nGRE, by virtue of a direct or indirect association with DNA-bound Oct-1, could play a role in hormone-dependent transcriptional repression of the GnRH gene. In contrast, Oct-1 does not appear to be a component of the GR-containing protein complex that is bound to the proximal nGRE.


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