Vitamin D receptor (VDR) is a transcription factor that mediates calcium absorption by intestinal epithelial cells. Although calcium absorption is canonically thought to occur only in the small intestine, recent studies have shown that VDR activity in the colon alone is sufficient to prevent calcium deficiency in mice. Here, we further investigate VDR activity in the colon. We assess VDR-DNA binding in mouse duodenal crypt, duodenal villi, and colonic epithelial cells using Chromatin Immunoprecipitation sequencing (ChIP-seq). We find that most VDR-responsive elements are common to all intestinal epithelial cells, though some VDR-responsive elements are regionally-enriched and exhibit greater VDR-binding affinity in either duodenal epithelial cells or colonic epithelial cells. We also assess chromatin accessibility in the same three cell types using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). By integrating the VDR ChIP-seq and ATAC-seq data, we find that regionally-enriched VDR-responsive elements exhibit greater chromatin accessibility in the region of their enrichment. Finally, we assess the transcription factor motifs present in VDR-responsive elements. We find that duodenum- and colon-enriched VDR-responsive elements exhibit different sets of transcription factor motifs other than VDR, suggesting that VDR may act together with different partner transcription factors in the two regions. Our work is the first investigation of VDR-DNA binding in the colon and provides a basis for further investigations of VDR activity in the colon.
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Copyright (c) 2021 Dennis A. Aldea, Rohit Aita, Sohaib Hassan, Evan S. Cohen, Joseph Hur, Oscar Pellón-Cárdenas, Lei Chen, Michael P. Verzi