Vitamin D receptor binding, chromatin states and association with multiple sclerosis
Human Molecular Genetics, 08/20/2012
Disanto G et al. – The data provide additional evidence for an important role played by B cells in multiple sclerosis (MS).Methods
- Authors aimed to investigate the relationship between vitamin D receptor (VDR) binding in lymphoblastoid cell lines (LCLs), chromatin states in LCLs and MS–associated genomic regions.
- Using the Genomic Hyperbrowser, they found that VDR–binding regions overlapped with active regulatory regions [active promoter (AP) and strong enhancer (SE)] in LCLs more than expected by chance [45.3–fold enrichment for SE (P < 2.0e–05) and 63.41–fold enrichment for AP (P < 2.0e–05)].
- Approximately 77% of VDR regions were covered by either AP or SE elements.
- The overlap between VDR binding and regulatory elements was significantly greater in LCLs than in non–immune cells (P < 2.0e–05).
- VDR binding also occurred within MS regions more than expected by chance (3.7–fold enrichment, P < 2.0e–05).
- Furthermore, regions of joint overlap SE–VDR and AP–VDR were even more enriched within MS regions and near to several disease–associated genes.
- These findings provide relevant insights into how vitamin D influences the immune system and the risk of MS through VDR interactions with the chromatin state inside MS regions.