Transcriptional regulation of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by glucocorticoids.
The 5'-flanking region [1892 base pairs (bp)] of the rat aryl sulfotransferase (SULT1A1) gene was cloned and the cis-acting sequences involved in glucocorticoid-inducible SULT1A1 gene transcription were characterized. SULT1A1 promoter and 5'-flanking sequences lacked a TATA box and a consensus glucocorticoid response element. Using a 5'-rapid amplification of cDNA ends approach, four SULT1A1 transcription start sites were identified. Transient transfection studies with SULT1A1-5':luciferase reporter constructs in primary cultured rat hepatocytes revealed that treatment with the potent glucocorticoid dexamethasone (10(-9)-10(-5) M) produced concentration-dependent increases in luciferase activity in constructs containing from 1892 to 119 bp of the SULT1A1 5'-flanking region. Relative to the most upstream SULT1A1 transcription start site, the minimal cis-acting sequences that were required for dexamethasone-inducible SULT1A1 expression were located between -84 and -69 bp. Treatment of transfectants with a panel of steroids, including dexamethasone, triamcinolone acetonide, hydrocortisone, dihydrotestosterone, 17beta-estradiol, and pregnenolone-16alpha-carbonitrile, revealed that steroid-inducible SULT1A1 gene expression was specific for glucocorticoid-class steroids. Concentration-response studies, coupled with a robust inhibition of glucocorticoid-inducible SULT1A1-5':luciferase reporter activity by antiglucocorticoid/antiprogestin RU-486, recapitulated earlier findings on endogenous SULT1A1 gene expression and implicated a major role for the glucocorticoid receptor transcription factor in the regulation of glucocorticoid-inducible SULT1A1 gene expression.
Duanmu
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Institute of Environmental Health Sciences, Wayne State University, 2727 Second Ave., Detroit, MI 48201, USA.
Kocarek
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TA
Runge-Morris
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M
D000818:Animals; D015239:Arylsulfotransferase / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006727:Hormone Antagonists / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008156:Luciferases / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D008969:Molecular Sequence Data; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D003907:Dexamethasone; D008156:Luciferases; D015239:Arylsulfotransferase