coup transcription factor i


Summary: A COUP transcription factor that was originally identified as a homodimer that binds to a direct repeat regulatory element in the chicken albumin promoter. It is a transcription factor that plays an important role in EMBRYONIC DEVELOPMENT of the CENTRAL NERVOUS SYSTEM.

Top Publications

  1. Tang L, Alger H, Lin F, Pereira F. Dynamic expression of COUP-TFI and COUP-TFII during development and functional maturation of the mouse inner ear. Gene Expr Patterns. 2005;5:587-92 pubmed
  2. Tang L, Alger H, Pereira F. COUP-TFI controls Notch regulation of hair cell and support cell differentiation. Development. 2006;133:3683-93 pubmed
  3. Le Dily F, Métivier R, Gueguen M, Le Péron C, Flouriot G, Tas P, et al. COUP-TFI modulates estrogen signaling and influences proliferation, survival and migration of breast cancer cells. Breast Cancer Res Treat. 2008;110:69-83 pubmed
    ..These results suggest that COUP-TFI selectively regulates the expression of endogenous E2-target genes and consequently modifies ER alpha positive mammary cells response to E2. ..
  4. Ben Shushan E, Sharir H, Pikarsky E, Bergman Y. A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells. Mol Cell Biol. 1995;15:1034-48 pubmed
  5. Jonk L, de Jonge M, Pals C, Wissink S, Vervaart J, Schoorlemmer J, et al. Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors. Mech Dev. 1994;47:81-97 pubmed
    ..Furthermore, strong ARP-1 expression was detected in lung and kidney. Our data strongly suggest an important role for the members of the COUP-family in the hormonal control of gene expression regulating embryogenesis. ..
  6. Zhou C, Qiu Y, Pereira F, Crair M, Tsai S, Tsai M. The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons. Neuron. 1999;24:847-59 pubmed
    ..These results also substantiate COUP-TFI as an important regulator of neuronal development and differentiation. ..
  7. Tsai S, Tsai M. Chick ovalbumin upstream promoter-transcription factors (COUP-TFs): coming of age. Endocr Rev. 1997;18:229-40 pubmed
  8. Piñon M, Tuoc T, Ashery Padan R, Molnar Z, Stoykova A. Altered molecular regionalization and normal thalamocortical connections in cortex-specific Pax6 knock-out mice. J Neurosci. 2008;28:8724-34 pubmed publisher
    ..Our findings indicate that Pax6 expression gradients in cortical progenitors do not directly impart thalamocortical or corticofugal areal identity. ..
  9. Tomassy G, De Leonibus E, Jabaudon D, Lodato S, Alfano C, Mele A, et al. Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI. Proc Natl Acad Sci U S A. 2010;107:3576-81 pubmed publisher
    ..Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. ..

More Information


  1. Klinge C. Role of estrogen receptor ligand and estrogen response element sequence on interaction with chicken ovalbumin upstream promoter transcription factor (COUP-TF). J Steroid Biochem Mol Biol. 1999;71:1-19 pubmed
    ..We suggest that COUP-TFI plays a role in mitigating estrogen-responsive gene expression. ..
  2. Kurihara I, Shibata H, Kobayashi S, Suda N, Ikeda Y, Yokota K, et al. Ubc9 and Protein Inhibitor of Activated STAT 1 Activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated Human CYP11B2 Gene Transcription. J Biol Chem. 2005;280:6721-30 pubmed
    ..Our data support a physiological role of Ubc9 and PIAS1 as transcriptional coactivators in COUP-TFI-mediated CYP11B2 transcription...
  3. Yamaguchi H, Zhou C, Lin S, Durand B, Tsai S, Tsai M. The nuclear orphan receptor COUP-TFI is important for differentiation of oligodendrocytes. Dev Biol. 2004;266:238-51 pubmed
    ..Taken together, these results suggest that COUP-TFI is an important regulator of oligodendrocyte differentiation. ..
  4. Garel S, Huffman K, Rubenstein J. Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants. Development. 2003;130:1903-14 pubmed
    ..Overall, our study demonstrates the role of endogenous Fgf8 in regulating early gradients of transcription factors in cortical progenitor cells and in molecular regionalization of the cortical plate. ..
  5. Yang C, Yu B, Zhou D, Chen S. Regulation of aromatase promoter activity in human breast tissue by nuclear receptors. Oncogene. 2002;21:2854-63 pubmed
    ..By binding to S1, ERalpha down-regulates the aromatase promoter activity. These results demonstrate that nuclear receptors play important roles in modulating aromatase expression in human breast tissue. ..
  6. Zhang L, Liu X, Gafken P, Kioussi C, Leid M. A chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) complex represses expression of the gene encoding tumor necrosis factor alpha-induced protein 8 (TNFAIP8). J Biol Chem. 2009;284:6156-68 pubmed publisher
    ..Together, these studies identify a novel COUP-TFI complex that functions as a repressor of transcription and may play a role in the TNFalpha signaling pathways. ..
  7. Naka H, Nakamura S, Shimazaki T, Okano H. Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development. Nat Neurosci. 2008;11:1014-23 pubmed publisher
    ..These findings reveal a part of the timer mechanisms for generating diverse types of neurons and glial cells during CNS development. ..
  8. Brown K, Alkuraya F, Matos M, Robertson R, Kimonis V, Morton C. NR2F1 deletion in a patient with a de novo paracentric inversion, inv(5)(q15q33.2), and syndromic deafness. Am J Med Genet A. 2009;149A:931-8 pubmed publisher
    ..Additionally, this study further highlights the need for high resolution analysis of clinical samples with chromosomal rearrangements as associated deletions may be primarily responsible for the clinical features of these patients. ..
  9. Dai K, Hussain M. NR2F1 disrupts synergistic activation of the MTTP gene transcription by HNF-4? and HNF-1?. J Lipid Res. 2012;53:901-8 pubmed publisher
    ..In this mechanism, NR2F1 does not affect activities of individual transcription factors; instead, it abrogates synergistic activation by HNF-4? and HNF-1 proteins. ..
  10. Wang L, Tsai S, Cook R, Beattie W, Tsai M, O Malley B. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989;340:163-6 pubmed
    ..We conclude that this superfamily of gene regulators contains proteins which bind and activate distal promoter elements of eukaryotic genes. ..
  11. Klinge C, Silver B, Driscoll M, Sathya G, Bambara R, Hilf R. Chicken ovalbumin upstream promoter-transcription factor interacts with estrogen receptor, binds to estrogen response elements and half-sites, and inhibits estrogen-induced gene expression. J Biol Chem. 1997;272:31465-74 pubmed
  12. Feng J, Chen D, Cooney A, Tsai M, Harris M, Tsai S, et al. The mouse bone morphogenetic protein-4 gene. Analysis of promoter utilization in fetal rat calvarial osteoblasts and regulation by COUP-TFI orphan receptor. J Biol Chem. 1995;270:28364-73 pubmed
    ..This suggests that COUP-TFI could act as a silencer for BMP-4 transcription in vivo. ..
  13. Job C, Tan S. Constructing the mammalian neocortex: the role of intrinsic factors. Dev Biol. 2003;257:221-32 pubmed
    ..Extrinsic influences appear to generate receptive fields for peripheral input, the summation of which determines the areal extent of particular neocortical region. ..
  14. Armentano M, Chou S, Tomassy G, Leingartner A, O Leary D, Studer M. COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nat Neurosci. 2007;10:1277-86 pubmed
    ..We conclude that COUP-TFI is required for balancing patterning of neocortex into frontal/motor and sensory areas by acting in its expression domain to repress frontal/motor area identities and to specify sensory area identities. ..
  15. Faedo A, Tomassy G, Ruan Y, Teichmann H, Krauss S, Pleasure S, et al. COUP-TFI coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT, and beta-catenin signaling. Cereb Cortex. 2008;18:2117-31 pubmed publisher
    ..We suggest that COUP-TFI controls these processes by repressing Mapk/Erk, Akt, and beta-catenin signaling. ..
  16. Zhuang Y, Gudas L. Overexpression of COUP-TF1 in murine embryonic stem cells reduces retinoic acid-associated growth arrest and increases extraembryonic endoderm gene expression. Differentiation. 2008;76:760-71 pubmed publisher
    ..Our results revealed for the first time that COUP-TF1 is an important signaling molecule during vitamin A (Rol)-mediated very early stage of embryonic development. ..
  17. Métivier R, Gay F, Hübner M, Flouriot G, Salbert G, Gannon F, et al. Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by MAPK. EMBO J. 2002;21:3443-53 pubmed
    ..These data indicate an alternative interaction process between nuclear receptors and demonstrate a novel protein intercommunication pathway that modulates hER alpha AF-1. ..
  18. Klinge C, Kaur K, Swanson H. The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1. Arch Biochem Biophys. 2000;373:163-74 pubmed
  19. Salas R, Petit F, Pipaon C, Tsai M, Tsai S. Induction of chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI ) gene expression is mediated by ETS factor binding sites. Eur J Biochem. 2002;269:317-25 pubmed
    ..In addition, COUP-TFI is coexpressed with some ETS factors in the mouse embryo. These results indicate that members of the ETS family can activate COUP-TFI gene expression. ..
  20. Zhou C, Tsai S, Tsai M. COUP-TFI: an intrinsic factor for early regionalization of the neocortex. Genes Dev. 2001;15:2054-9 pubmed
    ..Our results substantiate that COUP-TFI, an intrinsic factor, may work in concert with Pax6 and Emx2 to specify neocortical identity. ..
  21. Connor H, Nornes H, Neuman T. Expression screening reveals an orphan receptor chick ovalbumin upstream promoter transcription factor I as a regulator of neurite/substrate-cell contacts and cell aggregation. J Biol Chem. 1995;270:15066-70 pubmed
    ..Our data suggest that COUP-TF transcription factors are involved in the regulation of cell surface molecules during neruogenesis. ..
  22. Qiu Y, Pereira F, DeMayo F, Lydon J, Tsai S, Tsai M. Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. Genes Dev. 1997;11:1925-37 pubmed
    ..Furthermore, mCOUP-TFI possesses vital physiological functions that are distinct from mCOUP-TFII despite of their high degree of homology and extensive overlapping expression patterns. ..
  23. Rohr O, Schwartz C, Hery C, Aunis D, Tardieu M, Schaeffer E. The nuclear receptor chicken ovalbumin upstream promoter transcription factor interacts with HIV-1 Tat and stimulates viral replication in human microglial cells. J Biol Chem. 2000;275:2654-60 pubmed
    ..These results suggest that COUP-TF is an essential transcription factor involved in HIV-1 expression in microglia and reveal a novel interplay of Tat and COUP-TF during regulation of viral expression. ..
  24. Istrate M, Nussler A, Eichelbaum M, Burk O. Regulation of CYP3A4 by pregnane X receptor: The role of nuclear receptors competing for response element binding. Biochem Biophys Res Commun. 2010;393:688-93 pubmed publisher
    ..In summary, our results demonstrate that nuclear receptor binding to PXR response elements interferes with PXR-mediated expression and induction of CYP3A4 and thereby contributes to the interindividual variability of induction. ..
  25. Wang J, Park J, Drissi H, Wang X, Xu R. Epigenetic regulation of miR-302 by JMJD1C inhibits neural differentiation of human embryonic stem cells. J Biol Chem. 2014;289:2384-95 pubmed publisher
  26. Ip B, Wappler I, Peters H, Lindsay S, Clowry G, Bayatti N. Investigating gradients of gene expression involved in early human cortical development. J Anat. 2010;217:300-11 pubmed publisher
  27. Chan S, Xu N, Niemeyer C, Bone J, Flytzanis C. SpCOUP-TF: a sea urchin member of the steroid/thyroid hormone receptor family. Proc Natl Acad Sci U S A. 1992;89:10568-72 pubmed
    ..Transcripts derived from the S. purpuratus COUP-TF homologous gene were detected in ovarian and embryonic RNAs from various stages...
  28. Messager M, Carriere C, Bertagna X, de Keyzer Y. RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome. Eur J Endocrinol. 2006;154:159-66 pubmed
    ..Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation. ..
  29. Rada Iglesias A, Bajpai R, Prescott S, Brugmann S, Swigut T, Wysocka J. Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest. Cell Stem Cell. 2012;11:633-48 pubmed publisher
    ..Our results provide global insights into human NC chromatin landscapes and a rich resource for studies of craniofacial development and disease...
  30. Buholzer C, Arrighi J, Abraham S, Piguet V, Capponi A, Casal A. Chicken ovalbumin upstream promoter-transcription factor is a negative regulator of steroidogenesis in bovine adrenal glomerulosa cells. Mol Endocrinol. 2005;19:65-75 pubmed
    ..These results suggest that COUP-TF exerts a tonic inhibition on steroidogenesis by repressing StAR protein expression and that activators of aldosterone biosynthesis lift this inhibition in part by repressing COUP-TF levels. ..
  31. Zhang Y, Dufau M. Gene silencing by nuclear orphan receptors. Vitam Horm. 2004;68:1-48 pubmed
  32. Yu X, Mertz J. Distinct modes of regulation of transcription of hepatitis B virus by the nuclear receptors HNF4alpha and COUP-TF1. J Virol. 2003;77:2489-99 pubmed
    ..Thus, HNF4alpha and COUP-TF1 function through different mechanisms to regulate expression of the HBV genes. ..
  33. Kerber B, Fellert S, Hoch M. Seven-up, the Drosophila homolog of the COUP-TF orphan receptors, controls cell proliferation in the insect kidney. Genes Dev. 1998;12:1781-6 pubmed
    ..Seven-up in turn is capable of regulating the transcription of cell cycle regulators. ..
  34. Berrodin T, Marks M, Ozato K, Linney E, Lazar M. Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein. Mol Endocrinol. 1992;6:1468-78 pubmed
  35. Matharu P, Sweeney G. Cloning and sequencing of a COUP transcription factor gene expressed in Xenopus embryos. Biochim Biophys Acta. 1992;1129:331-4 pubmed
  36. Zhang Z, Zhou Y, Mendelsohn N, Bauer G, Strauss A. Regulation of the human long chain acyl-CoA dehydrogenase gene by nuclear hormone receptor transcription factors. Biochim Biophys Acta. 1997;1350:53-64 pubmed
    ..We conclude that the developmental and tissue-specific regulation of the human LCAD gene is mediated, in part, by these nuclear hormone receptor transcription factors. ..
  37. Anderson G, Larson R, Oas D, Sandhofer C, Schwartz H, Mariash C, et al. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) modulates expression of the Purkinje cell protein-2 gene. A potential role for COUP-TF in repressing premature thyroid hormone action in the developing brain. J Biol Chem. 1998;273:16391-9 pubmed
  38. Armentano M, Filosa A, Andolfi G, Studer M. COUP-TFI is required for the formation of commissural projections in the forebrain by regulating axonal growth. Development. 2006;133:4151-62 pubmed
  39. Suh J, Yu C, Tang K, Tanaka T, Kodama T, Tsai M, et al. The expression profiles of nuclear receptors in the developing and adult kidney. Mol Endocrinol. 2006;20:3412-20 pubmed
    ..Our results suggest that these nuclear receptors are likely to play important physiological roles in the kidney development. ..
  40. Navab R, Wang Y, Chow Y, Wang A, Jankov R, Takamoto N, et al. Regulation of human Clara cell 10 kD protein expression by chicken ovalbumin upstream promoter transcription factors (COUP-TFs). Am J Respir Cell Mol Biol. 2002;27:273-85 pubmed
    ..These experiments suggest that COUP-TFs may play a pivotal role in cell specificity of the human CC10 gene by inhibiting its expression in nonpermissive cells. ..
  41. Hegardt F. Transcriptional regulation of mitochondrial HMG-CoA synthase in the control of ketogenesis. Biochimie. 1998;80:803-6 pubmed
    ..Other transcription factors such as chicken ovalbumin upstream promoter transcription factor (COUP-TF) and hepatocyte nuclear factor 4 (HNF-4) compete for the PPRE site, modulating the response of PPAR. ..
  42. Yu R, Ito M, Jameson J. The murine Dax-1 promoter is stimulated by SF-1 (steroidogenic factor-1) and inhibited by COUP-TF (chicken ovalbumin upstream promoter-transcription factor) via a composite nuclear receptor-regulatory element. Mol Endocrinol. 1998;12:1010-22 pubmed
    ..We propose that Dax-1 is stimulated by SF-1, and that SF-1 and COUP-TF provide antagonistic pathways that converge upon a common regulatory site. ..
  43. Tambyrajah W, Doran E, Wood J, McGivan J. The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone. Arch Biochem Biophys. 2004;431:252-60 pubmed
  44. Liu Y, Brent G. A complex deoxyribonucleic acid response element in the rat Ca(2+)/calmodulin-dependent protein kinase IV gene 5'-flanking region mediates thyroid hormone induction and chicken ovalbumin upstream promoter transcription factor 1 repression. Mol Endocrinol. 2002;16:2439-51 pubmed
    ..COUP-TF1 binding did not influence TR/retinoid X receptor binding but modestly augmented RAR/retinoid X receptor binding. A single element confers T(3) and COUP-TF1 regulation of CaMKIV expression. ..
  45. Rohr O, Aunis D, Schaeffer E. COUP-TF and Sp1 interact and cooperate in the transcriptional activation of the human immunodeficiency virus type 1 long terminal repeat in human microglial cells. J Biol Chem. 1997;272:31149-55 pubmed
    ..These findings reveal how the novel interplay of Sp1 and COUP-TF families of transcription factors regulate HIV-1 gene expression. ..
  46. Qiu Y, Krishnan V, Zeng Z, Gilbert D, Copeland N, Gibson L, et al. Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes. Genomics. 1995;29:240-6 pubmed
    ..Furthermore, we mapped human COUP-TF I to 5q14 of chromosome 5 and COUP-TF II to 15q26 of chromosome 15. The results demonstrate that COUP-TF genes are located in chromosomal regions that are syntenic between mouse and human. ..
  47. Liu Y, Nakatani T, Kogai T, Mody K, Brent G. Thyroid hormone and COUP-TF1 regulate kallikrein-binding protein (KBP) gene expression. Endocrinology. 2011;152:1143-53 pubmed publisher
    ..COUP-TF1 may be an important factor to modulate expression of genes that are repressed by T(3). ..
  48. Thompson V, Day T, Bianco Miotto T, Selth L, Han G, Thomas M, et al. A gene signature identified using a mouse model of androgen receptor-dependent prostate cancer predicts biochemical relapse in human disease. Int J Cancer. 2012;131:662-72 pubmed publisher
    ..2, p = 0.038). We believe that our findings support the value of this novel mouse model of prostate cancer to identify candidate therapeutic targets and/or biomarkers of human disease. ..
  49. Wehrenberg U, Ivell R, Walther N. The COUP transcription factor (COUP-TF) is directly involved in the regulation of oxytocin gene expression in luteinizing bovine granulosa cells. Biochem Biophys Res Commun. 1992;189:496-503 pubmed
    ..These experimental results from in vitro and in vivo studies point to the direct involvement of COUP-TF in oxytocin gene down-regulation during luteinization of bovine granulosa cells. ..
  50. Parisot J, Flore G, Bertacchi M, Studer M. COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression. Development. 2017;144:2045-2058 pubmed publisher
    ..Together, our results indicate that COUP-TFI is required predominantly in DG progenitors for modulating expression of the Cxcr4 receptor during granule cell neurogenesis and migration. ..
  51. Boutros P, Yan R, Moffat I, Pohjanvirta R, Okey A. Transcriptomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in liver: comparison of rat and mouse. BMC Genomics. 2008;9:419 pubmed publisher
    ..Taken together, these data suggest that both rat and mouse models should be used to screen the acute hepatotoxic effects of drugs and toxic compounds. ..
  52. Murakami M, Ito H, Hagiwara K, Yoshida K, Sobue S, Ichihara M, et al. ATRA inhibits ceramide kinase transcription in a human neuroblastoma cell line, SH-SY5Y cells: the role of COUP-TFI. J Neurochem. 2010;112:511-20 pubmed publisher
    ..These results suggest that COUP-TFI was the ATRA-responsive suppressive transcription factor of CERK gene transcription. ..
  53. Le Page Y, Demay F, Salbert G. A neural-specific splicing event generates an active form of the Wiskott-Aldrich syndrome protein. EMBO Rep. 2004;5:895-900 pubmed
    ..Furthermore, expression of the truncated protein in PC12 cells, as well as in primary neurons, stimulates neuritogenesis. These data underscore the importance of the neural-specific splicing of WASP RNA during development. ..