Transcription activation by the orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI). Definition of the domain involved in the glucocorticoid response of the phosphoenolpyruvate carboxykinase gene.
Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs), orphan members of the nuclear receptor superfamily, play a key role in the regulation of organogenesis, neurogenesis, and cellular differentiation during embryogenic development. COUP-TFs are also involved in the regulation of several genes that encode metabolic enzymes. Although COUP-TFs function as potent transcription repressors, there are at least three different molecular mechanisms of activation of gene expression by COUP-TFs. First, as we have previously shown, COUP-TF is required as an accessory factor for the complete induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. This action is mediated by the binding of COUP-TF to the glucocorticoid accessory factor 1 (gAF1) and 3 (gAF3) elements in the phosphoenolpyruvate carboxykinase gene glucocorticoid response unit. In addition, COUP-TF1 binds to DNA elements in certain genes and transactivates directly. Finally, COUP-TF1 serves as a coactivator through DNA-bound hepatic nuclear factor 4. Here we show that the same region of COUP-TFI, located between amino acids 184 and 423, is involved in these three mechanisms of transactivation by COUP-TFI. Furthermore, we show that GRIP1 and SRC-1 potentiate the activity of COUP-TFI and that COUP-TFI associates with these coactivators in vivo using the same region required for transcription activation. Finally, overexpression of GRIP1 or SRC-1 does not convert COUP-TFI from a transcriptional repressor into a transcriptional activator in HeLa cells.
Sugiyama
T
T
Department of Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Wang
J C
JC
Scott
D K
DK
Granner
D K
DK
D000818:Animals; D051838:COUP Transcription Factor I; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D010047:Ovalbumin / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; C497589:NR2F1 protein, human; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D010047:Ovalbumin