MECHANISM OF CAMP REGULATION OF RENIN GENE-TRANSCRIPTION BY PROXIMAL PROMOTER

被引:32
作者
TAMURA, K
UMEMURA, S
YAMAGUCHI, S
IWAMOTO, T
KOBAYASHI, S
FUKAMIZU, A
MURAKAMI, K
ISHII, M
机构
[1] YOKOHAMA CITY UNIV,SCH MED,DEPT MED 2,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN
[2] UNIV TSUKUBA,INST APPL BIOCHEM,TSUKUBA,IBARAKI 305,JAPAN
关键词
RENIN; CAMP; TRANSCRIPTIONAL ACTIVATION; PROXIMAL PROMOTER; NUCLEAR FACTOR;
D O I
10.1172/JCI117547
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Renin is produced mainly by the kidney, and cAMP is a main positive regulator of its synthesis. This study was undertaken to analyze the molecular mechanism of cAMP-mediated regulation of Ren-1C gene transcription by the proximal promoter. We first showed that the promoter region from -365 to +16 of the mouse renin gene (Ren-1C) mediated the cAMP-induced chloramphenicol acetyltransferase gene expression in embryonic kidney-derived 293 cells. Deletion analysis and heterologous promoter assay disclosed that the proximal promoter region from -75 to +16 was able to activate chloramphenicol acetyltransferase expression by cAMP, and indicated that the proximal promoter element from -75 to -47 (RP-2 element) overlapping the TATA-like region was able to confer cAMP responsiveness. Electrophoretic mobility shift assay and DNase I footprinting analysis demonstrated that novel nuclear factors in 293 cells interacted with the RP-2 element, and that cAMP increased the binding activity of these nuclear factors to the RP-2 element. Furthermore, we demonstrated that cAMP enhanced the binding of nuclear factors derived from juxtaglomerular cells, the main production site of renin in the kidney, to the RP-2 element in vivo. These results suggest that the RP-2 element plays an important role in the cAMP-mediated regulation of Ren-1C gene transcription through the proximal promoter.
引用
收藏
页码:1959 / 1967
页数:9
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