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-responsive enhancer elements (CREs) in the promoter region of this gene. Regions from the 5'-flanking sequences of the gene were placed in a promoterless vector with a chloramphenicol acetyltransferase (CAT) reporter 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 endogenous promoter region. Within the upstream sequences there is a putative "core sequence" homologous to the eight base CRE consensus palindrome, but this region did not function independently as a CRE enhancer; additional upstream sequences were required to provide significant enhancer activity in response to cAMP. Regulation of expression of the alpha 2A-adrenergic gene by cAMP is complex and involves multiple and likely novel DNA sequences.