Transcriptional and posttranscriptional mechanisms regulate human renin gene expression in Calu-6 cells. Am J Physiol 1996 Jul;271(1 Pt 2):F94-100
Date
07/01/1996Pubmed ID
8760248DOI
10.1152/ajprenal.1996.271.1.F94Scopus ID
2-s2.0-0029759107 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
We have recently identified a human pulmonary carcinoma cell line (Calu-6) that expresses human renin (hREN) mRNA endogenously, and we use it herein as a model to examine the regulation of the hREN gene. Transfection analysis of a deletion series (-2750 to -149) of hREN promoter-luciferase fusion constructs revealed the presence of multiple weak regulatory elements within the first 1,301 bp of the 5'-flanking region and a classic silencer element within the first intron (intron A) of the gene. The 5'-flanking regulatory domain consisted of three closely linked elements, two negative and one positive, each contributing a cell-specific threefold modulation of transcriptional activity. Treating Calu-6 cells with forskolin caused a 100-fold increase in steady-state endogenous hREN mRNA but no increase in hREN promoter activity in transient transfections or in nuclear runoff transcription assays. Nevertheless, de novo transcription and translation were necessary for adenosine 3',5'-cyclic monophosphate (cAMP)-mediated induction. Our results suggest that multiple regulatory elements regulate basal transcriptional activity of the hREN gene and the increase in hREN mRNA by cAMP may be mediated by posttranscriptional mechanisms.
Author List
Lang JA, Ying LH, Morris BJ, Sigmund CDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Base SequenceCyclic AMP
Gene Expression Regulation
Gene Expression Regulation, Enzymologic
Humans
Molecular Probes
Molecular Sequence Data
Protein Processing, Post-Translational
RNA, Messenger
Renin
Transcription, Genetic
Tumor Cells, Cultured
