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(Received for publication, February 4, 1997, and in revised form, May 15, 1997)
From the Steroid hormone receptors and Stat factors
comprise two distinct families of inducible transcription factors.
Activation of a member of each family, namely the glucocorticoid
receptor by glucocorticoids and Stat5 by prolactin, is required for the
efficient induction of the expression of milk protein genes in the
mammary epithelium. We have studied the mode of interaction between
Stat5 and the glucocorticoid receptor in the activation of
Volume 272, Number 33,
Issue of August 15, 1997
pp. 20954-20960
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
-Casein Gene
Transcription
,
,
,
,
Institut für Medizinische Chemie und
Biochemie, Universität Innsbruck, Fritz-Pregl-Straße 3, A-6020
Innsbruck, Austria and the § Department of Medical
Nutrition, Karolinska Institute, Huddinge University Hospital F60,
Novum, S-14186 Huddinge, Sweden
-casein gene transcription. The functional role of potential half-palindromic glucocorticoid receptor-binding sites mapped previously in the promoter
region was investigated. -Casein gene promoter chloramphenicol acetyltransferase constructs containing mutations and deletions in
these sites were tested for their responsiveness to the synergistic effect of prolactin and dexamethasone employing COS-7 cells or HC11
mammary epithelial cells. Synergism depended on promoter regions
containing intact binding sites for the glucocorticoid receptor and
Stat5. The carboxyl-terminal transactivation domains of Stat5a and
Stat5b were not required for this synergism. Our results suggest that
in lactogenic hormone response elements glucocorticoid receptor
molecules bound to nonclassical half-palindromic sites gain competence
as transcriptional activators by the interaction with Stat5 molecules
binding to vicinal sites.
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