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环磷酸腺苷（cAMP）通过近端启动子对肾素基因转录的调控机制

Mechanism of cAMP regulation of renin gene transcription by proximal promoter.

作者信息

Tamura K, Umemura S, Yamaguchi S, Iwamoto T, Kobayashi S, Fukamizu A, Murakami K, Ishii M

机构信息

Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.

出版信息

J Clin Invest. 1994 Nov;94(5):1959-67. doi: 10.1172/JCI117547.

DOI:10.1172/JCI117547
PMID:7962542
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC294613/
Abstract

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.

摘要

肾素主要由肾脏产生，而环磷酸腺苷（cAMP）是其合成的主要正向调节因子。本研究旨在分析近端启动子介导的cAMP对Ren-1C基因转录调控的分子机制。我们首先发现，小鼠肾素基因（Ren-1C）从-365至+16的启动子区域在源自胚胎肾的293细胞中介导了cAMP诱导的氯霉素乙酰转移酶基因表达。缺失分析和异源启动子检测表明，从-75至+16的近端启动子区域能够通过cAMP激活氯霉素乙酰转移酶表达，并表明与类TATA区域重叠的从-75至-47的近端启动子元件（RP-2元件）能够赋予cAMP反应性。电泳迁移率变动分析和DNase I足迹分析表明，293细胞中的新型核因子与RP-2元件相互作用，且cAMP增加了这些核因子与RP-2元件的结合活性。此外，我们证明cAMP增强了源自肾小球旁细胞（肾脏中肾素的主要产生部位）的核因子在体内与RP-2元件的结合。这些结果表明，RP-2元件在通过近端启动子介导的cAMP对Ren-1C基因转录的调控中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/29d12cbc494d/jcinvest00036-0263-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/0ecbed66e2a1/jcinvest00036-0259-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/9a3f8dbe79e5/jcinvest00036-0262-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/d76d2e17835c/jcinvest00036-0262-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/3ae173f57279/jcinvest00036-0263-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/29d12cbc494d/jcinvest00036-0263-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/0ecbed66e2a1/jcinvest00036-0259-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/bd46466dc46c/jcinvest00036-0260-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/b227ce2da8cf/jcinvest00036-0260-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/89f2cdfd54d6/jcinvest00036-0261-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/9a3f8dbe79e5/jcinvest00036-0262-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/d76d2e17835c/jcinvest00036-0262-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/3ae173f57279/jcinvest00036-0263-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/294613/29d12cbc494d/jcinvest00036-0263-b.jpg

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本文引用的文献

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