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(Received for publication, February 22, 1996, and in revised form, May 6, 1996)
From the We have identified two regions of the mouse
gonadotropin-releasing hormone (GnRH) promoter, one between
Volume 271, Number 34,
Issue of August 23, 1996
pp. 20412-20420
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
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
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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