Genome-wide Analysis of Vitamin D Receptor Binding By ChIP-Seq

We used ChIP-Seq to identify the genomic locations bound by the vitamin D receptor (VDR) in two lymphoblastoid cell lines (LCLs) (CEPH individuals GM10855 and GM10861 from the International HapMap Project) before and after calcitriol treatment for 36 hours. Immunoprecipitated DNA was sequenced using the Illumina Genome Analyzer II. Sequence reads (35 bases; 10-19 million quality-filtered reads/sample) were aligned to the human genome (NCBI Build 36.3) using ELAND software. The number of unique alignments ranged from 7.73 million to 14.32 million. Peaks were called in the aligned sequence data using a model-based analysis of ChIP-Seq (MACS) and compared with sequenced sonicated and amplified input DNA. In the samples not treated with calcitriol, the number of peaks ranged from 468 to 4538 (median 975, mean 1587), while in the calcitriol-treated samples the number of peaks was between 2560 and 7244 (median 4546, mean 4560). 65-75% of peaks of untreated samples were in promoters, while only 24-50% of peaks of calcitirol-treated samples were in promoters. This study provides a comprehensive map of VDR binding in lymphoblastoid cell lines.