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• W2108442029 startingPage "2440" @default.
• W2108442029 abstract "The candidate human tumor suppressor gene cyclin C is a primary target of the anti-proliferative hormone 1α,25-dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ], but binding sites for the 1α,25(OH) 2 D 3 receptor (VDR), so-called 1α,25(OH) 2 D 3 response elements (VDREs), have not yet been identified in the promoter of this gene. We screened various cancer cell lines by quantitative PCR and found that the 1α,25(OH) 2 D 3 inducibility of cyclin C mRNA expression, in relationship with the 24-hydroxylase ( CYP24 ) gene, was best in MCF-7 human breast cancer cells. To characterize the molecular mechanisms, we analyzed 8.4 kb of the cyclin C promoter by using chromatin immunoprecipitation assays (ChIP) with antibodies against acetylated histone 4, VDR and its partner receptor, retinoid X receptor (RXR). The histone 4 acetylation status of all 23 investigated regions of the cyclin C promoter did not change significantly in response to 1α,25(OH) 2 D 3 , but four independent promoter regions showed a consistent, 1α,25(OH) 2 D 3 -dependent association with VDR and RXR over a time period of 240 min. Combined in silico/in vitro screening identified in each of these promoter regions a VDRE and reporter gene assays confirmed their functionality. Moreover, re-ChIP assays monitored simultaneous association of VDR with RXR, coactivator, mediator and RNA polymerase II proteins on these regions. Since cyclin C protein is associated with those mediator complexes that display transcriptional repressive properties, this study contributes to the understanding of the downregulation of a number of secondary 1α,25(OH) 2 D 3 -responding genes." @default.
• W2108442029 created "2016-06-24" @default.
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• W2108442029 date "2005-04-28" @default.
• W2108442029 modified "2023-10-16" @default.
• W2108442029 title "Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter" @default.
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• W2108442029 doi "https://doi.org/10.1093/nar/gki502" @default.
• W2108442029 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1087898" @default.
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