scholarly journals Genome-wide principles of gene regulation by the vitamin D receptor and its activating ligand

2011 ◽  
Vol 347 (1-2) ◽  
pp. 3-10 ◽  
Author(s):  
J. Wesley Pike
2013 ◽  
Vol 19 (8) ◽  
pp. 1035-1045 ◽  
Author(s):  
Jun-ichi Satoh ◽  
Hiroko Tabunoki

Background: Vitamin D is a liposoluble vitamin essential for calcium metabolism. The ligand-bound vitamin D receptor (VDR), heterodimerized with retinoid X receptor, interacts with vitamin D response elements (VDREs) to regulate gene expression. Vitamin D deficiency due to insufficient sunlight exposure confers an increased risk for multiple sclerosis (MS). Objective: To study a protective role of vitamin D in multiple sclerosis (MS), it is important to characterize the global molecular network of VDR target genes (VDRTGs) in immune cells. Methods: We identified genome-wide VDRTGs collectively from two distinct chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets of VDR-binding sites derived from calcitriol-treated human cells of B cell and monocyte origins. We mapped short reads of next generation sequencing (NGS) data on hg19 with Bowtie, detected the peaks with Model-based Analysis of ChIP-Seq (MACS), and identified genomic locations by GenomeJack, a novel genome viewer for NGS platforms. Results: We found 2997 stringent peaks distributed on protein-coding genes, chiefly located in the promoter and the intron on VDRE DR3 sequences. However, the corresponding transcriptome data verified calcitriol-induced upregulation of only a small set of VDRTGs. The molecular network of 1541 calcitriol-responsive VDRTGs showed a significant relationship with leukocyte transendothelial migration, Fcγ receptor-mediated phagocytosis, and transcriptional regulation by VDR, suggesting a pivotal role of genome-wide VDRTGs in immune regulation. Conclusion: These results suggest the working hypothesis that persistent deficiency of vitamin D might perturb the complex network of VDRTGs in immune cells, being responsible for induction of an autoimmune response causative for MS.


Vitamin D ◽  
2018 ◽  
pp. 141-174
Author(s):  
J. Wesley Pike ◽  
Mark B. Meyer ◽  
Seong M. Lee ◽  
Melda Onal ◽  
Nancy A. Benkusky

2010 ◽  
Vol 20 (10) ◽  
pp. 1352-1360 ◽  
Author(s):  
S. V. Ramagopalan ◽  
A. Heger ◽  
A. J. Berlanga ◽  
N. J. Maugeri ◽  
M. R. Lincoln ◽  
...  

2016 ◽  
Vol 48 (11) ◽  
pp. 1396-1406 ◽  
Author(s):  
Jun Wang ◽  
Louise B Thingholm ◽  
Jurgita Skiecevičienė ◽  
Philipp Rausch ◽  
Martin Kummen ◽  
...  

2016 ◽  
Vol 1 (1) ◽  
pp. 12-21 ◽  
Author(s):  
O. A. Gromova ◽  
I. Y. Torshin ◽  
V. B. Spirichev

The article presents the results of the genome-wide bioinformatic analysis of the vitamin D receptor interactions with the human genome DNA. Using a biological system assay, biological roles of proteins were analyzed that are specifically associated with the impact of VDR receptor. Systematization of the biological roles of vitamin D opens broad and previously unexplored perspectives for pediatric applications of vitamin D preparations for the prevention and treatment of a wide range of diseases starting from the fetal stage and early childhood.


2015 ◽  
Vol 93 (5) ◽  
pp. 311-318 ◽  
Author(s):  
Carsten Carlberg ◽  
Ferdinand Molnár

Vitamin D3 is one of the few natural compounds that has, via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and the transcription factor vitamin D receptor (VDR), a direct effect on gene regulation. For efficiently applying the therapeutic and disease-preventing potential of 1,25(OH)2D3 and its synthetic analogs, the key steps in vitamin D signaling need to be understood. These are the different types of molecular interactions with the VDR, such as (i) the complex formation of VDR with genomic DNA, (ii) the interaction of VDR with its partner transcription factors, (iii) the binding of 1,25(OH)2D3 or its synthetic analogs within the ligand-binding pocket of the VDR, and (iv) the resulting conformational change on the surface of the VDR leading to a change of the protein–protein interaction profile of the receptor with other proteins. This review will present the latest genome-wide insight into vitamin D signaling, and will discuss its therapeutic implications.


Sign in / Sign up

Export Citation Format

Share Document