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(Received for publication, May 3, 1996, and in revised form, August 28, 1996)
From the Department of Pharmacology, School of Medicine, Case
Western Reserve University, Cleveland, Ohio 44106
The
Volume 271, Number 49,
Issue of December 6, 1996
pp. 31650-31656
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Subunit Gene Bind Similar
Proteins in Trophoblasts and Gonadotropes but Have Distinct Functional
Sequence Requirements
subunit gene encodes a common subunit
shared by all glycoprotein hormones. This single copy gene is expressed
in pituitary gonadotropes and thyrotropes of all mammals and in
placental trophoblasts of primates and horses. Tandem cAMP response
elements (CREs) in the promoter of the human gene are key mediators of
this pattern of cell-specific expression. Replacing the palindromic
CREs with non-primate variant CREs significantly attenuated activity in trophoblasts but not in gonadotropes. Furthermore, proteins binding the
palindromic CRE cross-reacted with antibodies for CREB, CREM, ATF1,
ATF2, and c-Jun, while proteins binding the variant CRE cross-reacted
only with ATF2 and c-Jun antibodies. The data suggest that ATF2 and
c-Jun can activate transcription through the CREs in gonadotropes but
not in trophoblasts. Additional analyses indicated that while promoters
with either palindromic or variant CREs have similar overall activity
in gonadotropes, the variant CREs make a much smaller contribution to
promoter activity than their palindromic counterparts. The weaker
contribution of the variant CREs is compensated by the activity of two
upstream elements present in the promoter. This compensation probably
occurs through an indirect mechanism, as the binding affinity of
proteins to the CRE is not influenced by the presence of these upstream
elements.
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