The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids.
Glucocorticoids stimulate hepatic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) gene expression, thereby increasing the rate of gluconeogenesis. The effect of glucocorticoids on PEPCK gene expression is mediated by a set of promoter elements collectively referred to as the glucocorticoid response unit. The response unit spans a 100-bp segment and includes two glucocorticoid receptor binding sites (GR1 and GR2) and two accessory factor binding sites (AF1 and AF2), all of which are required for a maximal glucocorticoid response. The AF1 element also serves as a retinoic acid response element and may be involved in developmental and tissue-specific expression of the gene. In this study we report that COUP-TF and HNF-4, two orphan members of the nuclear receptor superfamily, bind to the AF1 element and function as accessory factors for the glucocorticoid response of the PEPCK gene.
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615.
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D000818:Animals; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis*; D010750:Phosphoproteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D051557:Hepatocyte Nuclear Factor 4; C497591:Nr2f1 protein, rat; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011965:Receptors, Glucocorticoid; D017471:Receptors, Interferon; D014157:Transcription Factors; D010729:Phosphoenolpyruvate Carboxykinase (GTP)