coup transcription factors


Summary: A sub-family of steroid receptor-related orphan nuclear receptors that have specificity for a variety of DNA sequences related to AGGTCA. COUP transcription factors can heterodimerize with a variety of factors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; and VITAMIN D RECEPTORS.

Top Publications

  1. Senawong T, Peterson V, Avram D, Shepherd D, Frye R, Minucci S, et al. Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression. J Biol Chem. 2003;278:43041-50 pubmed
    ..These findings implicate SIRT1 as a histone H3/H4 deacetylase in mammalian cells and in transcriptional repression mediated by CTIP2. ..
  2. Leid M, Ishmael J, Avram D, Shepherd D, Fraulob V, Dolle P. CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis. Gene Expr Patterns. 2004;4:733-9 pubmed
  3. 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. ..
  4. Rohr O, Lecestre D, Chasserot Golaz S, Marban C, Avram D, Aunis D, et al. Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. J Virol. 2003;77:5415-27 pubmed
    ..These data highlight a new mechanism of Tat inactivation through subnuclear relocalization that may ultimately lead to inhibition of viral pathogenesis. ..
  5. Liu X, Huang X, Sigmund C. Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription. Circ Res. 2003;92:1033-40 pubmed
    ..1 cells. These data suggest that Ear2 is a negative modulator of renin gene transcription in As4.1 cells, and that the renin enhancer may actually encode a complex positive and negative regulator of transcription. ..
  6. Hermann Kleiter N, Gruber T, Lutz Nicoladoni C, Thuille N, Fresser F, Labi V, et al. The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity. Immunity. 2008;29:205-16 pubmed publisher
    ..Our study establishes NR2F6 as a transcriptional repressor of IL-17 expression in Th17-differentiated CD4(+) T cells in vitro and in vivo. ..
  7. Avram D, Fields A, Pretty On Top K, Nevrivy D, Ishmael J, Leid M. Isolation of a novel family of C(2)H(2) zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors. J Biol Chem. 2000;275:10315-22 pubmed
  8. You M, Fischer M, Cho W, Crabb D. Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: inhibition by cyclic AMP and COUP transcription factors. Arch Biochem Biophys. 2002;398:79-86 pubmed
    ..These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting. ..
  9. Gauchat D, Escriva H, Miljkovic Licina M, Chera S, Langlois M, Begue A, et al. The orphan COUP-TF nuclear receptors are markers for neurogenesis from cnidarians to vertebrates. Dev Biol. 2004;275:104-23 pubmed
    ..Hence, a cnidarian transcription factor can be active in vertebrate cells, implying that functional interactions between COUP-TF and other nuclear receptors were evolutionarily conserved. ..

More Information


  1. Navab R, Gonzalez Santos J, Johnston M, Liu J, Brodt P, Tsao M, et al. Expression of chicken ovalbumin upstream promoter-transcription factor II enhances invasiveness of human lung carcinoma cells. Cancer Res. 2004;64:5097-105 pubmed
    ..These results suggest that COUP-TFII may be considered as a new target for anticancer therapies. ..
  2. Park J, Tsai S, Tsai M. Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions. Keio J Med. 2003;52:174-81 pubmed
    ..Here we will review the molecular mechanism of COUP-TFs as repressors and activators. Also, we will review the known biological function of COUP-TFI during development and differentiation. ..
  3. Warnecke M, Oster H, Revelli J, Alvarez Bolado G, Eichele G. Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception. Genes Dev. 2005;19:614-25 pubmed
    ..We propose that neurons in the dorsal division of LC contribute to the regulation of the forebrain clock, at least in part, through targeted release of noradrenaline into the cortical area. ..
  4. 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. ..
  5. Chu K, Zingg H. The nuclear orphan receptors COUP-TFII and Ear-2 act as silencers of the human oxytocin gene promoter. J Mol Endocrinol. 1997;19:163-72 pubmed
  6. Bailey P, Sartorelli V, Hamamori Y, Muscat G. The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD. Nucleic Acids Res. 1998;26:5501-10 pubmed
  7. Avram D, Ishmael J, Nevrivy D, Peterson V, Lee S, Dowell P, et al. Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2. J Biol Chem. 1999;274:14331-6 pubmed
    ..Heterodimeric interactions between ARP1 and Ear2 may define a distinct pathway of orphan receptor signaling. ..
  8. 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. ..
  9. Dougherty D, Park H, Sanders M. Interferon regulatory factors (IRFs) repress transcription of the chicken ovalbumin gene. Gene. 2009;439:63-70 pubmed publisher
    ..These experiments indicate that the repressor activity associated with the CAR site is mediated by IRF family members and suggest that IRF members also repress Ov in non-oviduct tissues. ..
  10. Lewis K, Drossopoulou G, Paton I, Morrice D, Robertson K, Burt D, et al. Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway. Development. 1999;126:2397-407 pubmed
    ..We also describe genetic mapping of gli1, ptc, shh and smoothened in chickens and confirm by co-segregation analysis that none of these genes correspond to talpid3. ..
  11. Liberati C, Cera M, Secco P, Santoro C, Mantovani R, Ottolenghi S, et al. Cooperation and competition between the binding of COUP-TFII and NF-Y on human epsilon- and gamma-globin gene promoters. J Biol Chem. 2001;276:41700-9 pubmed
    ..At the 5' site, COUP-TFII might cooperate with NF-Y, forming a stable complex, and stimulate transcription; at the 3' site, COUP-TFII might compete for binding with NF-Y and, directly or indirectly, decrease gene activity. ..
  12. Shi M, Hu Z, Zheng M, Song N, Huang Y, Zhao G, et al. Notch-Rbpj signaling is required for the development of noradrenergic neurons in the mouse locus coeruleus. J Cell Sci. 2012;125:4320-32 pubmed publisher
    ..Thus, our results provide the first evidence that Rbpj functions as a key modulator of LC neuron development by regulating Ascl1 expression directly, and indirectly through its target gene Hes1. ..
  13. Kobayashi S, Shibata H, Kurihara I, Yokota K, Suda N, Saito I, et al. Ubc9 interacts with chicken ovalbumin upstream promoter-transcription factor I and represses receptor-dependent transcription. J Mol Endocrinol. 2004;32:69-86 pubmed
    ..Our studies indicate that Ubc9 functions as a novel COUP-TFI corepressor, the function of which is distinct from its SUMO-1 conjugating enzyme activity. ..
  14. Sylvester I, Scholer H. Regulation of the Oct-4 gene by nuclear receptors. Nucleic Acids Res. 1994;22:901-11 pubmed
    ..Specifically, important roles for ARP-1 and RAR in Oct-4 expression are indicated. ..
  15. Giansily Blaizot M, Lopez E, Viart V, Chafa O, Tapon Bretaudiere J, Claustres M, et al. Lethal factor VII deficiency due to novel mutations in the F7 promoter: functional analysis reveals disruption of HNF4 binding site. Thromb Haemost. 2012;108:277-83 pubmed publisher
    ..Only then can an accurate molecular diagnosis be made and further genetic counselling and prenatal diagnosis be offered. ..
  16. Ahn J, Guarino L, Zhu Salzman K. Seven-up facilitates insect counter-defense by suppressing cathepsin B expression. FEBS J. 2007;274:2800-14 pubmed
  17. Huuskonen J, Vishnu M, Chau P, Fielding P, Fielding C. Liver X receptor inhibits the synthesis and secretion of apolipoprotein A1 by human liver-derived cells. Biochemistry. 2006;45:15068-74 pubmed
    ..These data indicate that LXR can be a significant negative regulator of apo A1 transcription and HDL synthesis. ..
  18. You L, Lin F, Lee C, DeMayo F, Tsai M, Tsai S. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature. 2005;435:98-104 pubmed
    ..Thus, COUP-TFII has a critical role in repressing Notch signalling to maintain vein identity, which suggests that vein identity is under genetic control and is not derived by a default pathway. ..
  19. Ladias J, Karathanasis S. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science. 1991;251:561-5 pubmed
    ..In cotransfection experiments, ARP-1 downregulated the apoAI gene. The involvement of ARP-1 in the regulation of apoAI gene expression suggests that it may participate in lipid metabolism and cholesterol homeostasis. ..
  20. Duffy D, Frank U. Modulation of COUP-TF expression in a cnidarian by ectopic Wnt signalling and allorecognition. PLoS ONE. 2011;6:e19443 pubmed publisher
    b>COUP transcription factors are required for the regulation of gene expression underlying development, differentiation, and homeostasis...
  21. De Martino M, Bhattachryya N, Alesci S, Ichijo T, Chrousos G, Kino T. The glucocorticoid receptor and the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II interact with and mutually affect each other's transcriptional activities: implications for intermediary metabolism. Mol Endocrinol. 2004;18:820-33 pubmed
    ..These interactions influence the transcription of both COUP-TFII- and GRalpha-responsive target genes, seem to be promoter specific, and can be in either a positive or negative direction. ..
  22. Mietus Snyder M, Sladek F, Ginsburg G, Kuo C, Ladias J, Darnell J, et al. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol. 1992;12:1708-18 pubmed
    ..These findings suggest that the transcription of the apoCIII gene in vivo is dependent, at least in part, upon the intracellular balance of these positive and negative regulatory factors. ..
  23. Antoniou E, Womack J, Grosz M. Synteny mapping of five human chromosome 7 genes on bovine chromosomes 4 and 21. Cytogenet Cell Genet. 1999;84:121-4 pubmed
    ..This study confirms the synteny conservation between HSA 7 and BTA 4, finely maps the breakpoints of conserved synteny on HSA 7 and defines a new synteny conservation between HSA 7 and BTA 21. ..
  24. Krizhanovsky V, Soreq L, Kliminski V, Ben Arie N. Math1 target genes are enriched with evolutionarily conserved clustered E-box binding sites. J Mol Neurosci. 2006;28:211-29 pubmed
    ..Our findings may be useful to the study of other bHLH transcription factors, many of which control the development of the nervous system. ..
  25. Dabrowski M, Aerts S, Kaminska B. Prediction of a key role of motifs binding E2F and NR2F in down-regulation of numerous genes during the development of the mouse hippocampus. BMC Bioinformatics. 2006;7:367 pubmed
  26. Castro J, Torres M, Sovino H, Fuentes A, Boric M, Johnson M. P450Arom induction in isolated control endometrial cells by peritoneal fluid from women with endometriosis. Fertil Steril. 2010;94:2521-7 pubmed publisher
  27. Li A, Xu X, Wang H, Chen G. [Study on inhibitory effect of medicated serum of SLW on estrogen production by human endometrial cells of endometriosis]. Zhongguo Zhong Yao Za Zhi. 2008;33:686-90 pubmed
  28. Xing W, Danilovich N, Sairam M. Orphan receptor chicken ovalbumin upstream promoter transcription factors inhibit steroid factor-1, upstream stimulatory factor, and activator protein-1 activation of ovine follicle-stimulating hormone receptor expression via composite cis-elements. Biol Reprod. 2002;66:1656-66 pubmed
    ..These data suggest a mechanism by which positive and negative regulators compete for the common regulatory elements, providing antagonistic pathways that might govern the expression of FSHR in gonadal cells. ..
  29. Hou S, Guan H, Ricciardi R. In adenovirus type 12 tumorigenic cells, major histocompatibility complex class I transcription shutoff is overcome by induction of NF-kappaB and relief of COUP-TFII repression. J Virol. 2002;76:3212-20 pubmed
  30. Wang Y, Zhang Y, Hillgartner F. Chicken ovalbumin upstream-promoter transcription factor and E-box-binding proteins enhance thyroid-hormone responsiveness of the malic enzyme gene in avian hepatocytes. Biochem J. 2002;361:391-400 pubmed
  31. Pereira F, Tsai M, Tsai S. COUP-TF orphan nuclear receptors in development and differentiation. Cell Mol Life Sci. 2000;57:1388-98 pubmed
    ..This defines the COUP-TFs as important factors in regulation of development and differentiation in multiple organisms. ..
  32. Wang Q, Bai Z, Xuan L, Hou L, Zhang B. Inhibitory role of transcription factor COUP-TFII in expression of hTERT in HeLa cells. Chin Med Sci J. 2004;19:157-63 pubmed
    ..The human COUP-TFII can firmly bind to hTERT promoter, and inhibit telomerase activity through decreasing hTERT transcription. It will greatly facilitate understanding of telomerase regulation in normal and cancer cells. ..
  33. Hermann Kleiter N, Meisel M, Fresser F, Thuille N, Muller M, Roth L, et al. Nuclear orphan receptor NR2F6 directly antagonizes NFAT and ROR?t binding to the Il17a promoter. J Autoimmun. 2012;39:428-40 pubmed publisher
    ..Taken together, our findings uncover an example of antagonistic regulation of Il17a transcription through the direct reciprocal actions of NR2F6 versus NFAT and ROR?t. ..
  34. Satoh S, Tang K, Iida A, Inoue M, Kodama T, Tsai S, et al. The spatial patterning of mouse cone opsin expression is regulated by bone morphogenetic protein signaling through downstream effector COUP-TF nuclear receptors. J Neurosci. 2009;29:12401-11 pubmed publisher
    ..Based on these findings, we propose a new molecular cascade involving BMP and COUP-TFs that conveys dorsoventral information to direct the expression of cone opsins during retinal development. ..
  35. Jiang X, Norman M, Roth L, Li X. Protein-DNA array-based identification of transcription factor activities regulated by interaction with the glucocorticoid receptor. J Biol Chem. 2004;279:38480-5 pubmed
    ..In this study, IRF and E47 were identified as participants in GRalpha cross-talk for the first time. This new finding expands our understanding of the functional role of GRalpha in the context of gene expression regulation. ..
  36. Strom A, Westin S, Eguchi H, Gustafsson J, Mode A. Characterization of orphan nuclear receptor binding elements in sex-differentiated members of the CYP2C gene family expressed in rat liver. J Biol Chem. 1995;270:11276-81 pubmed
    ..Our data indicate that the HPF1 elements in the rat CYP2C genes have limited functional importance and that HNF-4 is not a major trans-activator for any of these genes. ..
  37. Lutz B, Kuratani S, Cooney A, Wawersik S, Tsai S, Eichele G, et al. Developmental regulation of the orphan receptor COUP-TF II gene in spinal motor neurons. Development. 1994;120:25-36 pubmed
    ..Collectively, our studies raise the possibility that cCOUP-TF II is involved in motor neuron development. ..
  38. Waltner Law M, Duong D, Daniels M, Herzog B, Wang X, Prasad R, et al. Elements of the glucocorticoid and retinoic acid response units are involved in cAMP-mediated expression of the PEPCK gene. J Biol Chem. 2003;278:10427-35 pubmed
    ..This provides a further illustration of how the PEPCK gene promoter integrates different hormone responses through overlapping HRUs that utilize some of the same transcription factors and coactivators. ..
  39. Musio A, Montagna C, Zambroni D, Indino E, Barbieri O, Citti L, et al. Inhibition of BUB1 results in genomic instability and anchorage-independent growth of normal human fibroblasts. Cancer Res. 2003;63:2855-63 pubmed
    ..Our data suggest that chromosomal instability and aneuploidy are early changes that precede tumorigenicity in the multistep process leading to neoplastic transformation. ..
  40. Yang D, Rosenberg H, Chen Q, Dyer K, Kurosaka K, Oppenheim J. Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. Blood. 2003;102:3396-403 pubmed
    ..Thus, EDN and its mouse ortholog, mEAR2, are eosinophil granule-derived antimicrobial RNases that function as chemoattractants for DCs in vitro and in vivo. ..
  41. Sato Y, Suzuki T, Hidaka K, Sato H, Ito K, Ito S, et al. Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle. J Clin Endocrinol Metab. 2003;88:3415-20 pubmed
    ..These results indicated that DAX-1 and COUP-TFII may play a role in the modulation of Ad4BP/SF-1-dependent transcription of steroidogenic enzymes in different cell types and follicular stages in normal cycling human ovaries. ..
  42. Rowntree R, Harris A. DNA polymorphisms in potential regulatory elements of the CFTR gene alter transcription factor binding. Hum Genet. 2002;111:66-74 pubmed
    ..Both of the polymorphisms altered DNA-protein binding, as shown by electrophoretic mobility shift assays (EMSA). These changes in transcription factor binding at a putative regulatory region could influence CFTR gene expression. ..
  43. Togawa T, Shofuda K, Yaginuma T, Tomino S, Nakato H, Izumi S. Structural analysis of gene encoding cuticle protein BMCP18, and characterization of its putative transcription factor in the silkworm, Bombyx mori. Insect Biochem Mol Biol. 2001;31:611-20 pubmed
    ..Bmsvp bound to the 12-bp sequence in vitro, suggesting that Bmsvp regulates the BMCP18 gene expression. ..
  44. Shibata H, Ikeda Y, Morohashi K, Mukai T, Kurihara I, Ando T, et al. Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors. Endocr Res. 2000;26:1039-44 pubmed
  45. Yamamoto M, Fujinuma M, Tanaka M, Drager U, McCaffery P. Sagittal band expression of COUP-TF2 gene in the developing cerebellum. Mech Dev. 1999;84:143-6 pubmed
    ..By postnatal day 5 the COUP-TF2 expression substantially decreases to low, but detectable, levels. ..
  46. Pereira F, Qiu Y, Zhou G, Tsai M, Tsai S. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev. 1999;13:1037-49 pubmed
    ..This down-regulation suggests that COUP-TFII may be required for bidirectional signaling between the endothelial and mesenchymal compartments essential for proper angiogenesis and heart development. ..
  47. Weatherford E, Liu X, Sigmund C. Regulation of renin expression by the orphan nuclear receptors Nr2f2 and Nr2f6. Am J Physiol Renal Physiol. 2012;302:F1025-33 pubmed publisher
    ..We conclude that both Nr2f2 and Nr2f6 negatively regulate renin promoter activity, but may do so by divergent mechanisms. ..
  48. 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. ..
  49. Cabrero A, Merlos M, Laguna J, Carrera M. Down-regulation of acyl-CoA oxidase gene expression and increased NF-kappaB activity in etomoxir-induced cardiac hypertrophy. J Lipid Res. 2003;44:388-98 pubmed
    ..Overall, the findings here presented show that etomoxir treatment may induce cardiac hypertrophy via increased cellular oxidative stress and NF-kappaB activation. ..
  50. Bandukwala H, Sundrud M, Rao A. Orphans against autoimmunity. Immunity. 2008;29:167-8 pubmed publisher
    ..In this issue of Immunity, Hermann-Kleiter et al. (2008) identify a nuclear orphan receptor, NR2F6, as a negative regulator of the T helper 17 cell subset and report that NR2F6-deficient mice develop late-onset autoimmune disease. ..
  51. Burke L, Downes M, Carozzi A, Giguere V, Muscat G. Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis. Nucleic Acids Res. 1996;24:3481-9 pubmed
    ..In conclusion, our studies identified a potent transcriptional repression domain in RVR, characterized critical amino acids within the silencing region and provide evidence for the physiological role of RVR during myogenesis. ..
  52. Eckley D, Schroer T. Interactions between the evolutionarily conserved, actin-related protein, Arp11, actin, and Arp1. Mol Biol Cell. 2003;14:2645-54 pubmed
    ..Arp11 significantly decreases the formation of these organized Arp1 assemblies. Finally, this assay was used to confirm the identity of a putative Arp11 homolog in Drosophila melanogaster. ..
  53. Konoshita T, Makino Y, Wakahara S, Ido K, Yoshida M, Kawai Y, et al. Candidate cis-elements for human renin gene expression in the promoter region. J Cell Biochem. 2004;93:327-36 pubmed
    ..Further functional characterization of these elements would provide important data for a better understanding of human renin gene expression. ..