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.
Hall
R K
RK
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615.
Sladek
F M
FM
Granner
D K
DK
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)