PT - JOURNAL ARTICLE AU - Ursula Ehmer AU - Sandra Kalthoff AU - Tim O. Lankisch AU - Nicole Freiberg AU - Michael P. Manns AU - Christian P. Strassburg TI - Shared Regulation of <em>UGT1A7</em> by Hepatocyte Nuclear Factor (HNF) 1α and HNF4α AID - 10.1124/dmd.109.030403 DP - 2010 Jul 01 TA - Drug Metabolism and Disposition PG - 1246--1257 VI - 38 IP - 7 4099 - http://dmd.aspetjournals.org/content/38/7/1246.short 4100 - http://dmd.aspetjournals.org/content/38/7/1246.full SO - Drug Metab Dispos2010 Jul 01; 38 AB - Substrates for glucuronidation include endogenous and xenobiotic compounds such as environmental carcinogens and drugs, as well as the chemotherapeutic agent irinotecan. The UDP-glucuronosyltransferase (UGT) 1A7 gene is expressed in the upper gastrointestinal tract and the lung but is not expressed in the liver. The transcriptional regulation of UGT1A7 and the putative influence of single nucleotide polymorphisms (SNPs) are incompletely characterized. UGT1A8, UGT1A9, and UGT1A10, which are highly homologous to UGT1A7, have been reported to be transcriptionally regulated by hepatocyte nuclear factors (HNFs). In this study, we show the activation of UGT1A7 by the aforementioned transcription factors. Sequence analyses, mutagenesis, reporter gene experiments, small interfering RNA silencing, chromatin immunoprecipitation, and electromobility shift assays identified five HNF binding sites in the proximal promoter region of UGT1A7 that were regulated by HNF1α and HNF4α. Activation by HNF1α was lower in the presence of the UGT1A7 −57G SNP. In contrast to liver-expressed UGT1A9, transcriptional activation of UGT1A7 by HNF4α was lower and dependent on higher HNF4α concentrations, which may contribute to the observed differences in tissue expression patterns. Therefore, a specific role of HNF in the transcriptional control of UGT1A7 is shown and characterized, which may contribute to its tissue specificity and function. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics