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• W2009281643 endingPage "1257" @default.
• W2009281643 startingPage "1246" @default.
• W2009281643 abstract "Substrates for glucuronidation include endogenous and xenobiotic compounds such as environmental carcinogens and drugs, as well as the chemotherapeutic agent irinotecan. The UDP-glucuronosyltransferase (<i>UGT) 1A7</i> gene is expressed in the upper gastrointestinal tract and the lung but is not expressed in the liver. The transcriptional regulation of <i>UGT1A7</i> and the putative influence of single nucleotide polymorphisms (SNPs) are incompletely characterized. <i>UGT1A8</i>, <i>UGT1A9</i>, and <i>UGT1A10</i>, which are highly homologous to <i>UGT1A7</i>, have been reported to be transcriptionally regulated by hepatocyte nuclear factors (HNFs). In this study, we show the activation of <i>UGT1A7</i> 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 <i>UGT1A7</i> 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 <i>UGT1A9</i>, transcriptional activation of <i>UGT1A7</i> 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 <i>UGT1A7</i> is shown and characterized, which may contribute to its tissue specificity and function." @default.
• W2009281643 created "2016-06-24" @default.
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• W2009281643 date "2010-04-20" @default.
• W2009281643 modified "2023-09-23" @default.
• W2009281643 title "Shared Regulation of <i>UGT1A7</i> by Hepatocyte Nuclear Factor (HNF) 1α and HNF4α" @default.
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• W2009281643 doi "https://doi.org/10.1124/dmd.109.030403" @default.
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