RT Journal
A1 Ramagopalan, Sreeram V.
A1 Heger, Andreas
A1 Berlanga, Antonio J.
A1 Maugeri, Narelle J.
A1 Lincoln, Matthew R.
A1 Burrell, Amy
A1 Handunnetthi, Lahiru
A1 Handel, Adam E.
A1 Disanto, Giulio
A1 Orton, Sarah-Michelle
A1 Watson, Corey T.
A1 Morahan, Julia M.
A1 Giovannoni, Gavin
A1 Ponting, Chris P.
A1 Ebers, George C.
A1 Knight, Julian C.
T1 A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution
JF Genome Research 
JO Genome Research 
YR 2010 
FD October 01 
VO 20 
IS 10 
SP 1352 
OP 1360 
DO 10.1101/gr.107920.110 
UL http://genome.cshlp.org/content/20/10/1352.abstract 
AB Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, remain poorly understood. We determined VDR binding throughout the human genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After calcitriol stimulation, we identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near autoimmune and cancer associated genes identified from genome-wide association (GWA) studies. Notable genes with VDR binding included IRF8, associated with MS, and PTPN2 associated with Crohn's disease and T1D. Furthermore, a number of single nucleotide polymorphism associations from GWA were located directly within VDR binding intervals, for example, rs13385731 associated with SLE and rs947474 associated with T1D. We also observed significant enrichment of VDR intervals within regions of positive selection among individuals of Asian and European descent. ChIP-seq determination of transcription factor binding, in combination with GWA data, provides a powerful approach to further understanding the molecular bases of complex diseases.