Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor
| Autor: | Jackie A. Fretz, Mark B. Meyer, Lee A. Zella, Sungtae Kim, Nirupama K. Shevde, Miwa Yamazaki, Makoto Watanuki, J. Wesley Pike |
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| Rok vydání: | 2007 |
| Předmět: |
Chromatin Immunoprecipitation
TRPV6 Endocrinology Diabetes and Metabolism Clinical Biochemistry Biology Response Elements Biochemistry Calcitriol receptor Article Histones Mice Endocrinology Gene expression Animals Humans Vitamin D Enhancer Molecular Biology Gene Conserved Sequence Oligonucleotide Array Sequence Analysis Regulation of gene expression Base Sequence RANK Ligand Cell Biology Cell biology Retinoid X Receptors Gene Expression Regulation Regulatory sequence Receptors Calcitriol Molecular Medicine RNA Polymerase II Chromatin immunoprecipitation |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 103:389-395 |
| ISSN: | 0960-0760 |
| Popis: | 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) functions as a systemic signal in vertebrate organisms to control the expression of genes whose products are vital to the maintenance of calcium and phosphorus homeostasis. This regulatory capability is mediated by the vitamin D receptor (VDR) which localizes at DNA sites adjacent to the promoter regions of target genes and initiates the complex events necessary for transcriptional modulation. Recent investigations using chromatin immunoprecipitation techniques combined with various gene scanning methodologies have revealed new insights into the location, structure and function of these regulatory regions. In the studies reported here, we utilized the above techniques to identify key enhancer regions that mediate the actions of vitamin D on the calcium ion channel gene TRPV6, the catabolic bone calcium-mobilizing factor gene RankL and the bone anabolic Wnt signaling pathway co-receptor gene LRP5. We also resolve the mechanism whereby 1,25(OH)2D3 autoregulates the expression of its own receptor. The results identify new features of vitamin D-regulated enhancers, including their locations at gene loci, the structure of the VDR binding sites located within, their modular nature and their functional activity. Our studies suggest that vitamin D enhancers regulate the expression of key target genes by facilitating the recruitment of both the basal transcriptional machinery as well as the protein complexes necessary for altered gene expression. |
| Databáze: | OpenAIRE |
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