title: Transcriptional regulation of human hydroxysteroid sulfotransferase SULT2A1 by LXRα.
abstract: 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.
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Mengxi
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Bingfang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Yixian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Meishu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Songrong
authors.initials: S
authors.lastname: Ren
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.).
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.) wex6@pitt.edu liusuhuan@gmail.com huangmin@mail.sysu.edu.en.
authors.forename: Suhuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.) wex6@pitt.edu liusuhuan@gmail.com huangmin@mail.sysu.edu.en.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Clinical Pharmacology, Sun Yat-Sen University, Guangzhou, China (Z.O., B.H., M.H.); Center for Pharmacogenetics and Department of Pharmaceutical Sciences (Z.O., M.J., B.H., Y.H., M.X., S.R., So.L., W.X.) and Department of Pharmacology and Chemical Biology (W.X.), University of Pittsburgh, Pittsburgh, Pennsylvania; and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China (Z.O., Su.L.) wex6@pitt.edu liusuhuan@gmail.com huangmin@mail.sysu.edu.en.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015238:Sulfotransferases / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D015238:Sulfotransferases; C028152:alcohol sulfotransferase