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  • Title: Identification of cyclic AMP response element in the human renin gene.
    Author: Smith DL, Morris BJ, Do YS, Law RE, Shaw KJ, Hseuh WA.
    Journal: Biochem Biophys Res Commun; 1994 Apr 15; 200(1):320-9. PubMed ID: 8166700.
    Abstract:
    In order to identify the mechanism by which cyclic AMP stimulates expression of the human renin gene (REN), the effect of forskolin was tested in transient expression analyses of REN 5'-flanking DNA-chloramphenicol acetyltransferase (CAT) reporter gene constructs in secondary cultures of human chorio-decidual cells, a major site of renin synthesis. Forskolin induced a mean 5-fold stimulation which was localized to DNA in the region -249 to -162 with respect to the transcription start site (+1). Such DNA also mediated a response to forskolin in heterologous (HSV thymidine kinase) promoter constructs. Strong cAMP-response element (CRE) homology at -222 to -218 resembled the target for members of the CRE binding protein (CREB) family. Gel shift assays demonstrated similarly migrating nucleoprotein complexes for oligonucleotides containing the putative REN CRE as for a canonical CRE, in chorio-decidual, JEG-3 and HeLa nuclear extracts. Mutation of residues critical for CREB attachment reduced binding. In conclusion, a CRE was identified at -222 to -218 that appears critical for cAMP-induced human renin gene transcription.
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