title: 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter.
abstract: We have shown that 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) down-regulates renin expression. To explore the molecular mechanism, we analyzed the mouse Ren-1c gene promoter by luciferase reporter assays. Deletion analysis revealed two DNA fragments from -2,725 to -2,647 (distal fragment) and from -117 to +6 (proximal fragment) that are sufficient to mediate the repression. Mutation of the cAMP response element (CRE) in the distal fragment blunted forskolin stimulation as well as 1,25(OH)(2)D(3) inhibition of the transcriptional activity, suggesting the involvement of CRE in 1,25(OH)(2)D(3)-induced suppression. EMSA revealed that 1,25(OH)(2)D(3) markedly inhibited nuclear protein binding to the CRE in the promoter. ChIP and GST pull-down assays demonstrated that liganded VDR blocked the binding of CREB to the CRE by directly interacting with CREB with the ligand-binding domain, and the VDR-mediated repression can be rescued by CREB, CBP, or p300 overexpression. These data indicate that 1,25(OH)(2)D(3) suppresses renin gene expression at least in part by blocking the formation of CRE-CREB-CBP complex.
authors: Department of Medicine, Division of Biological Sciences, the University of Chicago, Chicago, Illinois 60637, USA.
authors: Weihua
authors: W
authors: Yuan
authors: Wei
authors: W
authors: Pan
authors: Juan
authors: J
authors: Kong
authors: Wei
authors: W
authors: Zheng
authors: Frances L
authors: FL
authors: Szeto
authors: Kari E
authors: KE
authors: Wong
authors: Ronald
authors: R
authors: Cohen
authors: Anna
authors: A
authors: Klopot
authors: Zhongyi
authors: Z
authors: Zhang
authors: Yan Chun
authors: YC
authors: Li
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D006801:Humans; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012083:Renin / Q000096:biosynthesis / Q000235:genetics*; D020218:Response Elements; D015398:Signal Transduction
chemical_list: D002843:Chromatin; D008024:Ligands; D004247:DNA; D000242:Cyclic AMP; D012083:Renin; D002117:Calcitriol