Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 121, Issue 1-2, Pages 130-135Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2010.02.036
Keywords
Genome-wide analysis; ChIP-chip analysis; ChIP-seq analysis; VDR/RXR binding; Distal transcriptional regulation; Histone acetylation; RNA polymerase II recruitment; BAC clone evaluation
Funding
- NIAMS NIH HHS [R01 AR045173, R01 AR045173-05, AR-045173] Funding Source: Medline
- NIDDK NIH HHS [R01 DK074993-03, DK-073995, R01 DK074993-04, DK-074993, R01 DK072281-04, R01 DK072281, R01 DK073995, R01 DK074993-03S1, R01 DK072281-05, R01 DK073995-02, DK-072281, R01 DK074993] Funding Source: Medline
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1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) functions as a steroid hormone to modulate the expression of genes. Its actions are mediated by the vitamin D receptor (VDR) which binds to target genes and functions to recruit coregulatory complexes that are essential for transcriptional modulation. ChIP analysis coupled to tiled DNA microarray hybridization (ChIP-chip) or massively parallel DNA sequencing (ChIP-seq) is now providing critical new insight into how genes are regulated. In studies herein, we utilized these techniques as well as gene expression analysis to explore the actions of 1,25(OH)(2)D-3 at the genome-wide and individual target gene levels in cells. We identify a series of overarching principles that likely define the actions of 1,25(OH)(2)D-3 at most target genes. We discover that while VDR binding to target sites is ligand-dependent, RXR binding is ligand-independent. We also show that while VDR/RXR binding can localize to promoters, it occurs more frequently at multiple sites many kilobases from target gene promoters. We then describe a new method whereby the regulatory regions of complex genes can be evaluated using large recombineered bacterial artificial chromosomes. We conclude that these new approaches are likely to replace many of the traditional methods used to explore the regulation of transcription. (C) 2010 Elsevier Ltd. All rights reserved.
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