PT  - JOURNAL ARTICLE
AU  - Kathleen G Barrett
AU  - Hailin Fang
AU  - Thomas A Kocarek
AU  - Melissa Runge-Morris
TI  - Transcriptional Regulation of SULT1C2 by Vitamin D Receptor in LS180 Human Colorectal Adenocarcinoma Cells
AID  - 10.1124/dmd.116.070300
DP  - 2016 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.116.070300
4099  - http://dmd.aspetjournals.org/content/early/2016/04/29/dmd.116.070300.short
4100  - http://dmd.aspetjournals.org/content/early/2016/04/29/dmd.116.070300.full
AB  - The factors that regulate expression of genes in the 1C family of human cytosolic sulfotransferases (SULT1C) are not well understood. In a recent study evaluating the effects of a panel of transcription factor activators on SULT1C family member expression in LS180 human colorectal adenocarcinoma cells, we found that SULT1C2 expression was significantly increased by 1α,25-dihydroxyvitamin D3 (VitD3) treatment. The objective of the current study was to identify the mechanism responsible for VitD3-mediated activation of SULT1C2 transcription. VitD3 treatment of LS180 cells activated transcription of a transfected luciferase reporter plasmid that contained ~5Kb of the SULT1C2 gene, which included 402 nt of the non-coding exon 1, all of intron 1, and 21 nt of exon 2. Although computational analysis of the VitD3-responsive region of the SULT1C2 gene identified a pregnane X receptor (PXR)-binding site within exon 1, the transfected 5Kb SULT1C2 reporter was not activated by treatment with rifampicin, a prototypical PXR agonist. However, deletion or mutation of the predicted PXR-binding site abolished VitD3-mediated SULT1C2 transcriptional activation, identifying the site as a functional vitamin D response element (VDRE). We further demonstrated that vitamin D receptor (VDR) can interact directly with the SULT1C2 VDRE sequence using an ELISA-based transcription factor binding assay. In conclusion VitD3-inducible SULT1C2 transcription is mediated through a VDRE in exon 1. These results suggest a role for SULT1C2 in VitD3-regulated physiological processes in human intestine.