Journal
STEROIDS
Volume 78, Issue 2, Pages 127-136Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2012.10.019
Keywords
Chromatin; Gene regulation; Genome-wide view; Nuclear receptor; Vitamin D; Vitamin D receptor
Funding
- Academy of Finland
- Juselius Foundation
- National Institute of Health [R01 CA095367-06, 2R01-CA-095045-06]
- NCI Cancer Center Support Grant
- NucSys
- European Community FP6 Marie Curie Research Training Network
- CanSys, an Atlantis EU-US training program
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The main physiological actions of the biologically most active metabolite of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3), are calcium and phosphorus uptake and transport and thereby controlling bone formation. Other emergent areas of 1 alpha,25(OH)(2)D-3 action are in the control of immune functions, cellular growth and differentiation. All genomic actions of 1 alpha,25(OH)(2)D-3 are mediated by the transcription factor vitamin D receptor (VDR) that has been the subject of intense study since the 1980's. Thus, vitamin D signaling primarily implies the molecular actions of the VDR. In this review, we present different perspectives on the VDR that incorporate its role as transcription factor and member of the nuclear receptor superfamily, its dynamic changes in genome-wide locations and DNA binding modes, its interaction with chromatin components and its primary protein-coding and non-protein coding target genes and finally how these aspects are united in regulatory networks. By comparing the actions of the VDR, a relatively well-understood and characterized protein, with those of other transcription factors, we aim to build a realistic positioning of vitamin D signaling in the context of other intracellular signaling systems. (C) 2012 Elsevier Inc. All rights reserved.
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