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J Biol Chem, Vol. 275, Issue 11, 8114-8120, March 17, 2000
From the Departments of A growth hormone-inducible nuclear factor complex
(GHINF), affinity-purified using the growth hormone response element
(GHRE) from the promoter of rat serine protease inhibitor 2.1, was
found to contain Stat5a and -5b, as well as additional components. The ubiquitous transcription factor yin-yang 1 (YY1) is present in GHINF.
An antibody to YY1 inhibited the formation of the GHINF·GHRE complex
in an electrophoretic mobility shift assay. Furthermore, Stat5 was
co-immunoprecipitated from rat hepatic nuclear extracts with antibodies
to YY1. An examination of the GHRE shows that, in addition to two
Yin-yang 1 and Glucocorticoid Receptor Participate in the
Stat5-mediated Growth Hormone Response of the Serine Protease
Inhibitor 2.1 Gene*
,¶
Pediatrics and
§ Biochemistry, Molecular Biology, and Biophysics and the
¶ Institute of Human Genetics, University of Minnesota,
Minneapolis, Minnesota 55455
-activated sites, it contains a putative YY1 binding site between
the two -activated sites, overlapping them both. Mutation of this
putative YY1 site results in a decrease of GHINF·GHRE complex
formation in an electrophoretic mobility shift assay and a
corresponding decrease in growth hormone (GH) response in functional
assays. The glucocorticoid receptor was also present in GHINF, and
Stat5 co-immunoprecipitates with glucocorticoid receptor in hepatic
nuclear extracts from rats treated with GH. GH activation of serine
protease inhibitor 2.1 requires the unique sequence of the GHRE
encompassing the recognition sites of several transcription factors,
and the interaction of these factors enhances the assembly of the
transcription complex.
*
This work was supported by National Institutes of Health
Grant DK32817, the Genentech Foundation for Growth and Development, and
the Vikings Children's Fund.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Pediatrics, University of Minnesota, 420 Delaware St. S.E., Box 75, Minneapolis, MN 55455. Tel.: 612-624-7144; Fax: 612-624-2682; E-mail:
berry002@tc.umn.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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