PT  - JOURNAL ARTICLE
AU  - Sarah Dubaisi
AU  - Hailin Fang
AU  - Thomas A. Kocarek
AU  - Melissa Runge-Morris
TI  - Transcriptional Regulation of Human Cytosolic Sulfotransferase 1C3 by Peroxisome Proliferator-Activated Receptor γ in LS180 Human Colorectal Adenocarcinoma Cells
AID  - 10.1124/mol.116.106005
DP  - 2016 Jan 01
TA  - Molecular Pharmacology
PG  - mol.116.106005
4099  - http://molpharm.aspetjournals.org/content/early/2016/08/26/mol.116.106005.short
4100  - http://molpharm.aspetjournals.org/content/early/2016/08/26/mol.116.106005.full
AB  - Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is up-regulated by agonists of peroxisome proliferator-activated receptor (PPAR) α and γ. To determine the mechanism responsible for PPAR-mediated up-regulation, we prepared reporter plasmids containing fragments of the SULT1C3 5'-flanking region. During initial attempts to amplify a 2.8Kb fragment from different sources of human genomic DNA, a 1.9Kb fragment was sometimes co-amplified with the expected 2.8Kb fragment. Comparison of the 1.9Kb fragment sequence to the published SULT1C3 5'-flanking sequence revealed an 863nt deletion (nt -146 to -1008 relative to the transcription start site). Transfection analysis in LS180 cells demonstrated that PPARα, σ, and γ agonist treatments induced luciferase expression from a reporter plasmid containing the 2.8Kb but not the 1.9Kb fragment. The PPAR agonists also activated a 1Kb reporter containing the 863nt deletion region. Computational analysis identified three peroxisome proliferator response elements (PPREs) within the 863nt region, and serial deletions and site-directed mutations indicated that the most distal PPRE (at nt -769) was essential for obtaining PPAR-mediated transcriptional activation. Although agonists of all three PPARs could activate SULT1C3 transcription, RNA interference analysis indicated the predominance of PPARγ. These data demonstrate that the PPARγ regulatory network includes SULT1C3 and imply that this enzyme contributes to the control of such PPARγ-regulated intestinal processes as growth, differentiation, and metabolism.