THE CAMP RESPONSE ELEMENTS OF THE ALPHA-SUBUNIT GENE BIND SIMILAR PROTEINS IN TROPHOBLASTS AND GONADOTROPES BUT HAVE DISTINCT FUNCTIONAL SEQUENCE REQUIREMENTS

The alpha subunit gene encodes a common subunit shared by all glycopro tein hormones, This single copy gene is expressed in pituitary gonadot ropes and thyrotropes of all mammals and in placental trophoblasts of primates and horses. Tandem cAMP response elements (CREs) in the promo ter of the human gene are key mediators of this pattern of cell-specif ic expression. Replacing the palindromic CREs with non-primate variant CREs significantly attenuated activity in trophoblasts but not in gon adotropes, Furthermore, proteins binding the palin-dromic CRE cross-re acted with antibodies for CREB, CREM, ATF1, ATF2, and c-Jun, while pro teins binding the variant CRE cross-reacted only with ATF2 and c-Jun a ntibodies, The data suggest that ATF2 and c-Jun can activate transcrip tion through the CREs in gonadotropes but not in trophoblasts. Additio nal analyses indicated that while promoters with either palindromic or variant CREs have similar overall activity in gonadotropes, the varia nt CREs make a much smaller contribution to promoter activity than the ir palindromic counterparts, The weaker contribution of the variant CR Es is compensated by the activity of two upstream elements present in the promoter, This compensation probably occurs through an indirect me chanism, as the binding affinity of proteins to the CRE is not influen ced by the presence of these upstream elements.