ENHANCED TRANSCRIPTION OF THE HUMAN ALPHA(2A)-ADRENERGIC RECEPTOR GENE BY CAMP - EVIDENCE FOR MULTIPLE CAMP-RESPONSIVE SEQUENCES IN THE PROMOTER REGION OF THIS GENE

Expression of the human alpha(2A)-adrenergic receptor gene is induced by cAMP. The present studies were designed to define potential cAMP-re sponsive enhancer elements (CREs) in the promoter region of this gene. Regions from the 5'-flanking sequences of the gene were placed in a p romoterless vector with a chloramphenicol acetyltransferase (CAT) repo rter gene, and cAMP-stimulated CAT activity was assayed in transfected JEG-3 placental carcinoma cells. Enhancer activity responsive to cAMP was located in DNA sequences both upstream and downstream from the en dogenous promoter region. Within the upstream sequences there is a put ative ''core sequence'' homologous to the eight base CRE consensus pal indrome, but this region did not function independently as a CRE enhan cer; additional upstream sequences were required to provide significan t enhancer activity in response to cAMP. Regulation of expression of t he alpha(2A),-adrenergic gene by cAMP is complex and involves multiple and likely novel DNA sequences.