RT Journal Article
SR Electronic
T1 Transcriptional Regulation of Human Hydroxysteroid Sulfotransferase SULT2A1 by LXR<em>α</em>
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1684
OP 1689
DO 10.1124/dmd.114.058479
VO 42
IS 10
A1 Zhimin Ou
A1 Mengxi Jiang
A1 Bingfang Hu
A1 Yixian Huang
A1 Meishu Xu
A1 Songrong Ren
A1 Song Li
A1 Suhuan Liu
A1 Wen Xie
A1 Min Huang
YR 2014
UL http://dmd.aspetjournals.org/content/42/10/1684.abstract
AB The nuclear receptor liver X receptor (LXR) plays an important role in the metabolism and homeostasis of cholesterol, lipids, bile acids, and steroid hormones. In this study, we uncovered a function of LXRα (NR1H3) in regulating the human hydroxysteroid sulfotransferase SULT2A1, a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens. We showed that activation of LXR induced the expression of SULT2A1 at mRNA, protein, and enzymatic levels. A combination of promoter reporter gene and chromatin immunoprecipitation assays showed that LXRα transactivated the SULT2A1 gene promoter through its specific binding to the −500- to −258-base pair region of the SULT2A1 gene promoter. LXR small interfering RNA knockdown experiments suggested that LXRα, but not LXRβ, played a dominant role in regulating SULT2A1. In primary human hepatocytes, we found a positive correlation between the expression of SULT2A1 and LXRα, which further supported the regulation of SULT2A1 by LXRα. In summary, our results established human SULT2A1 as a novel LXRα target gene. The expression of LXRα is a potential predictor for the expression of SULT2A1 in human liver.