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.
Department of Medicine, Stanford University School of Medicine, California.
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L
Shilo
M
M
Sakaue
J M
JM
Thomas
M
M
Philip
B B
BB
Hoffman
D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002822:Choriocarcinoma / Q000201:enzymology / Q000235:genetics; D000242:Cyclic AMP / Q000235:genetics / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D018341:Receptors, Adrenergic, alpha-2; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase