title: Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan. satoj@my-pharm.ac.jp
authors: Jun-ichi
authors: J
authors: Satoh
authors: Hiroko
authors: H
authors: Tabunoki
mesh_terms: D047369:Chromatin Immunoprecipitation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014807:Vitamin D / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D030181:Vitamin D Response Element / Q000235:genetics / Q000276:immunology
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D
keywords: ChIP-Seq; GenomeJack; VDR; multiple sclerosis; pathway analysis; vitamin D