IBMS BoneKEy | Perspective
New techniques in transcription research extend our understanding of the molecular actions of the vitamin D hormone
J Wesley Pike
Mark B Meyer
Melissa L Martowicz
DOI:10.1138/20090376
Abstract
Interest in vitamin D and its hormonal derivative 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has increased in the past few years as a result of the hormone's general actions at the skeleton, but perhaps more so because of its potential ability to regulate cell growth and differentiation. These actions suggest a possible therapeutic role for the vitamin D hormone in a wide variety of diseases of growth control, immune function, and in cancer. The biological actions of 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR), which functions as a transcription factor at multiple target genes. Chromatin immunoprecipitation (ChIP) coupled to either tiled microarray analysis (ChIP-chip) or massive parallel sequencing (ChIP-seq) promises to revolutionize the field of transcriptional regulation. We discuss these techniques and their utility in the context of several vitamin D target genes including the Vdr, Cyp24a1 and the osteoclastogenic cytokine receptor activator of NF-κB ligand (Rankl). We find that 1,25(OH)2D3 and its receptor modulate the expression of these and other genes through multiple enhancers that are frequently located at remote sites many kilobases from their genes' transcriptional start sites.
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