Transcription Activation by the Orphan Nuclear Receptor, Chicken Ovalbumin Upstream Promoter-Transcription Factor I (COUP-TFI)

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.

[1]  D. Kardassis,et al.  Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3. , 1992, The Journal of biological chemistry.

[2]  D. Granner,et al.  The genes of hepatic glucose metabolism. , 1990, The Journal of biological chemistry.

[3]  H. Gronemeyer,et al.  The nuclear receptor ligand-binding domain: structure and function. , 1998, Current opinion in cell biology.

[4]  T. Yamamoto,et al.  Dual transcriptional control by Ear3/COUP: negative regulation through the DR1 direct repeat and positive regulation through a sequence downstream of the transcriptional start site of the mouse mammary tumor virus promoter. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[6]  I. Talianidis,et al.  Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression , 1997, Molecular and cellular biology.

[7]  Jeffrey A. Lefstin,et al.  Allosteric effects of DNA on transcriptional regulators , 1998, Nature.

[8]  S. Cereghini,et al.  Positive regulation of the vHNF1 promoter by the orphan receptors COUP-TF1/Ear3 and COUP-TFII/Arp1 , 1996, Molecular and cellular biology.

[9]  John A. Mitchell,et al.  Identification and Characterization of a Second Retinoic Acid Response Element in the Phosphoenolpyruvate Carboxykinase Gene Promoter (*) , 1996, The Journal of Biological Chemistry.

[10]  J. Gustafsson,et al.  Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene , 1990, Molecular and cellular biology.

[11]  J. Liu,et al.  Cyclic AMP induction of phosphoenolpyruvate carboxykinase (GTP) gene transcription is mediated by multiple promoter elements. , 1991, The Journal of biological chemistry.

[12]  D. Granner,et al.  SRC-1 and GRIP1 Coactivate Transcription with Hepatocyte Nuclear Factor 4* , 1998, The Journal of Biological Chemistry.

[13]  Philippe Kastner,et al.  Nonsteroid nuclear receptors: What Are genetic studies telling us about their role in real life? , 1995, Cell.

[14]  B. Paulweber,et al.  Functional domains of the human orphan receptor ARP-1/COUP-TFII involved in active repression and transrepression , 1997, Molecular and cellular biology.

[15]  M. Magnuson,et al.  Location and characterization of two widely separated glucocorticoid response elements in the phosphoenolpyruvate carboxykinase gene , 1988, Molecular and cellular biology.

[16]  R. O’Brien,et al.  A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Takiguchi,et al.  Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4). , 1993, The Journal of biological chemistry.

[18]  M. Tsai,et al.  Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. , 1997, Genes & development.

[19]  B. O’Malley,et al.  COUP transcription factor is a member of the steroid receptor superfamily , 1989, Nature.

[20]  A. Cooney,et al.  Molecular mechanisms of COUP-TF-mediated transcriptional repression: evidence for transrepression and active repression , 1996, Molecular and cellular biology.

[21]  R. Evans,et al.  The RXR heterodimers and orphan receptors , 1995, Cell.

[22]  Jameyla A. Ladias,et al.  Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily , 1991, Science.

[23]  A. Cooney,et al.  Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors. , 1993, The Journal of biological chemistry.

[24]  F. Hegardt,et al.  Chicken ovalbumin upstream-promoter transcription factor (COUP-TF) could act as a transcriptional activator or repressor of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene. , 1997, The Biochemical journal.

[25]  R. Hanson,et al.  Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. , 1997, Annual review of biochemistry.

[26]  C. Glass,et al.  Nuclear receptor coactivators. , 1997, Current opinion in cell biology.

[27]  F. Sladek,et al.  The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Stallcup,et al.  GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  R. O’Brien,et al.  Signal transduction convergence: phorbol esters and insulin inhibit phosphoenolpyruvate carboxykinase gene transcription through the same 10-base-pair sequence. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. Salbert,et al.  The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation , 1997, Molecular and cellular biology.

[31]  P. Chambon,et al.  RARs and RXRs: evidence for two autonomous transactivation functions (AF‐1 and AF‐2) and heterodimerization in vivo. , 1993, The EMBO journal.

[32]  J. Chiang,et al.  Orphan Receptors Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) and Retinoid X Receptor (RXR) Activate and Bind the Rat Cholesterol 7α-Hydroxylase Gene (CYP7A)* , 1997, The Journal of Biological Chemistry.

[33]  P. Monaci,et al.  Identification and characterization of hepatocyte-specific regulatory regions of the rat pyruvate kinase L gene. The synergistic effect of multiple elements. , 1990, The Journal of biological chemistry.

[34]  D. Aunis,et al.  Chicken Ovalbumin Upstream Promoter Transcription Factor, a Transcriptional Activator of HIV-1 Gene Expression in Human Brain Cells* , 1996, The Journal of Biological Chemistry.

[35]  J B Lawrence,et al.  Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. , 1994, Genes & development.

[36]  B. O’Malley,et al.  The COUP-TFs compose a family of functionally related transcription factors. , 1991, Gene expression.

[37]  John A. Mitchell,et al.  The Orphan Receptor COUP-TF Binds to a Third Glucocorticoid Accessory Factor Element within the Phosphoenolpyruvate Carboxykinase Gene Promoter* , 1996, The Journal of Biological Chemistry.

[38]  R J Fletterick,et al.  Structure and specificity of nuclear receptor-coactivator interactions. , 1998, Genes & development.

[39]  Michael R. Green,et al.  Transcription activation by the adenovirus E1a protein , 1989, Nature.

[40]  M. Garabedian,et al.  GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors , 1997, Molecular and cellular biology.

[41]  R. O’Brien,et al.  Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. , 1990, Science.

[42]  A. Cooney,et al.  Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors , 1992, Molecular and cellular biology.