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A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution

Sreeram V Ramagopalan1, Andreas Heger, Antonio J Berlanga

  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, United Kingdom. sreeramr@well.ox.ac.uk

Genome Research
|August 26, 2010
PubMed

Insights

Vitamin D

Area of Science:

  • Genomics
  • Molecular Biology
  • Endocrinology

Background:

  • Vitamin D's role extends beyond calcium homeostasis, impacting diverse biological processes.
  • The precise mechanisms of vitamin D action via the nuclear vitamin D receptor (VDR) and its link to diseases are not fully understood.

Purpose of the Study:

  • To map genome-wide VDR binding sites.
  • To identify genes regulated by vitamin D.
  • To correlate VDR binding with genetic associations for complex diseases.

Main Methods:

  • Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) to determine VDR binding.
  • Calcitriol stimulation to observe gene expression changes.
  • Integration of ChIP-seq data with genome-wide association (GWA) study data.

Main Results:

  • Identified 2776 genomic VDR binding sites and 229 vitamin D-responsive genes.
  • Enriched VDR binding near genes associated with autoimmune diseases and cancer.
  • Found VDR binding sites overlapping with single nucleotide polymorphisms (SNPs) linked to multiple sclerosis, Crohn's disease, type 1 diabetes, and lupus erythematosus.
  • Observed enrichment of VDR intervals in regions of positive selection in Asian and European populations.

Conclusions:

  • VDR plays a significant role in regulating genes involved in complex diseases.
  • ChIP-seq combined with GWA data offers a powerful method for dissecting the molecular basis of diseases.
  • Understanding VDR's genomic targets provides insights into vitamin D's pleiotropic effects and clinical relevance.

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