%0 Journal Article %A Hai-Lin Fang %A Stephen C. Strom %A Hongbo Cai %A Charles N. Falany %A Thomas A. Kocarek %A Melissa Runge-Morris %T Regulation of Human Hepatic Hydroxysteroid Sulfotransferase Gene Expression by the Peroxisome Proliferator-Activated Receptor α Transcription Factor %D 2005 %R 10.1124/mol.104.005389 %J Molecular Pharmacology %P 1257-1267 %V 67 %N 4 %X Human hydroxysteroid sulfotransferase or (HUMAN)SULT2A1 catalyzes the sulfonation of procarcinogen xenobiotics, hydroxysteroids, and bile acids and plays a dynamic role in hepatic cholesterol homeostasis. The treatment of primary cultured human hepatocytes with a peroxisome proliferator-activated receptor α (PPARα)-activating concentration of ciprofibrate (10- 4 M) increased (HUMAN)SULT2A1 mRNA, immunoreactive protein, and enzymatic activity levels by ∼2-fold. By contrast, expression of (RAT)SULT2A3, the rat counterpart to (HUMAN)SULT2A1, was induced by treatment of primary hepatocyte cultures with an activator of the pregnane X receptor, but not PPARα. In HepG2 cells, transient transfection analyses of luciferase reporter constructs containing upstream regions of the (HUMAN)SULT2A1 gene implicated a candidate peroxisome proliferator response element (PPRE) at nucleotides (nt) -5949 to -5929 relative to the transcription start site. Site-directed mutagenesis and electrophoretic mobility shift assay studies confirmed that this distal PPRE (dPPRE), a direct repeat nuclear receptor motif containing one intervening nt, represented a functional PPRE. Chromatin immunoprecipitation analysis indicated that the (HUMAN)SULT2A1 dPPRE was also a functional element in the context of the human genome. These data support a major role for the PPARα transcription factor in the regulation of hepatic (HUMAN)SULT2A1. Results also indicate that important species differences govern the transactivation of SULT2A gene transcription by nuclear receptors. %U https://molpharm.aspetjournals.org/content/molpharm/67/4/1257.full.pdf