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Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes.
Mult Scler 2013; 19(8):1035-45MS

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.

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.

Authors+Show Affiliations

Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan. satoj@my-pharm.ac.jpNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23401126

Citation

Satoh, Jun-ichi, and Hiroko Tabunoki. "Molecular Network of Chromatin Immunoprecipitation Followed By Deep Sequencing-based Vitamin D Receptor Target Genes." Multiple Sclerosis (Houndmills, Basingstoke, England), vol. 19, no. 8, 2013, pp. 1035-45.
Satoh J, Tabunoki H. Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes. Mult Scler. 2013;19(8):1035-45.
Satoh, J., & Tabunoki, H. (2013). Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes. Multiple Sclerosis (Houndmills, Basingstoke, England), 19(8), pp. 1035-45. doi:10.1177/1352458512471873.
Satoh J, Tabunoki H. Molecular Network of Chromatin Immunoprecipitation Followed By Deep Sequencing-based Vitamin D Receptor Target Genes. Mult Scler. 2013;19(8):1035-45. PubMed PMID: 23401126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes. AU - Satoh,Jun-ichi, AU - Tabunoki,Hiroko, Y1 - 2013/02/11/ PY - 2013/2/13/entrez PY - 2013/2/13/pubmed PY - 2014/3/1/medline KW - ChIP-Seq KW - GenomeJack KW - VDR KW - multiple sclerosis KW - pathway analysis KW - vitamin D SP - 1035 EP - 45 JF - Multiple sclerosis (Houndmills, Basingstoke, England) JO - Mult. Scler. VL - 19 IS - 8 N2 - 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. SN - 1477-0970 UR - https://www.unboundmedicine.com/medline/citation/23401126/Molecular_network_of_chromatin_immunoprecipitation_followed_by_deep_sequencing_based_vitamin_D_receptor_target_genes_ L2 - http://journals.sagepub.com/doi/full/10.1177/1352458512471873?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -