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Gene Review

Nr2f1  -  nuclear receptor subfamily 2, group F,...

Mus musculus

Synonyms: COUP transcription factor 1, COUP transcription factor I, COUP-TF I, COUP-TF1, COUP-TFI, ...
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Disease relevance of Nr2f1


High impact information on Nr2f1

  • Our results substantiate that COUP-TFI, an intrinsic factor, may work in concert with Pax6 and Emx2 to specify neocortical identity [5].
  • The spatial and temporal expression pattern of COUP-TFI suggested a role in specification of the neocortex and in maintaining cortical identity [5].
  • Altered region-specific expression of marker genes in the cortex as well as miswired area-specific connections between the cortex and the thalamus in COUP-TFI null mice indicate COUP-TFI plays a critical role in regulating early regionalization [5].
  • Multiple COUP-TF members have been cloned and they share a high degree of sequence homology between species as divergent as Drosophila and humans, suggesting a conservation of function through evolution [6].
  • COUP-TFI expression in ACTH-secreting tumor cells blocked retinoic acid action [7].

Biological context of Nr2f1


Anatomical context of Nr2f1


Associations of Nr2f1 with chemical compounds

  • We conclude that the antagonism by COUP-TF uncovers differential activation states of PPAR alpha/RXR alpha heterodimers in the absence and in the presence of 9-cis RA [12].
  • Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) genes encode transcription factors belonging to the orphan subfamily of the steroid/thyroid hormone receptor superfamily [15].
  • Likewise, overexpression of the COUP-TF expression vector blocked the estrogen-stimulated response of mERM in transfected cells [16].
  • In mammals, the COUP-TF-family consisting of two structurally related proteins, COUP-TFI and COUP-TFII belongs to the orphan member of the steroid/thyroid hormone receptor superfamily [17].
  • Following 2 days of RA treatment, increased binding of COUP-TF to the ARE7 oligomer also occurs [18].

Physical interactions of Nr2f1

  • By comparison, in nontumorigenic Ad5 cells, class I expression is high due to negligible binding of COUP-TF and strong binding of NF-kappaB [11].
  • Inhibitors of preadipocyte differentiation induce COUP-TF binding to a PPAR/RXR binding sequence [18].

Regulatory relationships of Nr2f1


Other interactions of Nr2f1

  • The DNA binding activities and nuclear expression of Sp1/3 and COUP-TF in normal fetal mouse heart were similar to those in the hypertrophied adult heart [21].
  • Here, we show that in the MZ, the nuclear receptor COUP-TFI is localized in calbindin-positive cells and not in reelin-positive cells [22].
  • Using this approach, we isolated clones encoding the orphan nuclear receptors chicken ovalbumin upstream promoter-transcription factor (COUP-TF) 2 and COUP-TF3 [23].
  • Taken together, these findings suggest that FOG-2 functions as a corepressor for both GATA and COUP-TF proteins [23].
  • The molecular mechanism of this repression is due to the competition between COUP-TF and the estrogen receptor for binding at identical contact sites in the overlapping region of the mERM [16].

Analytical, diagnostic and therapeutic context of Nr2f1

  • As a prototype for our analysis, we investigated the expression patterns of chicken ovalbumin upstream promoter transcription factor (COUP-TF) -I and -II in more details during embryonic development and in the adult by immunohistochemistry [8].
  • Next, with the help of transplantations and gain-of-function studies in organotypic cultures, we have shown that COUP-TFI and COUP-TFII are expressed in distinct and non-overlapping migratory routes [9].
  • COUP-TF I mRNA levels were reduced in the spinal cord ventricular zone (VZ) after treatment, whereas in the telencephalon, mRNA levels were unaffected in the VZ and increased in the intermediate zone (IZ) [24].
  • In contrast, high COUP-TFI expression impeded the neuronal differentiation of P19 cells induced with RA, resulting in cell cultures lacking neurons [25].


  1. Chicken ovalbumin upstream promoter-transcription factors and their regulation. Qiu, Y., Krishnan, V., Pereira, F.A., Tsai, S.Y., Tsai, M.J. J. Steroid Biochem. Mol. Biol. (1996) [Pubmed]
  2. 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. Kadowaki, Y., Toyoshima, K., Yamamoto, T. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Association of histone deacetylase with COUP-TF in tumorigenic Ad12-transformed cells and its potential role in shut-off of MHC class I transcription. Smirnov, D.A., Hou, S., Ricciardi, R.P. Virology (2000) [Pubmed]
  4. Orphan receptor COUP-TF I antagonizes retinoic acid-induced neuronal differentiation. Neuman, K., Soosaar, A., Nornes, H.O., Neuman, T. J. Neurosci. Res. (1995) [Pubmed]
  5. COUP-TFI: an intrinsic factor for early regionalization of the neocortex. Zhou, C., Tsai, S.Y., Tsai, M.J. Genes Dev. (2001) [Pubmed]
  6. Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. Qiu, Y., Pereira, F.A., DeMayo, F.J., Lydon, J.P., Tsai, S.Y., Tsai, M.J. Genes Dev. (1997) [Pubmed]
  7. Retinoic acid prevents experimental Cushing syndrome. Páez-Pereda, M., Kovalovsky, D., Hopfner, U., Theodoropoulou, M., Pagotto, U., Uhl, E., Losa, M., Stalla, J., Grübler, Y., Missale, C., Arzt, E., Stalla, G.K. J. Clin. Invest. (2001) [Pubmed]
  8. The expression profiles of nuclear receptors in the developing and adult kidney. Suh, J.M., Yu, C.T., Tang, K., Tanaka, T., Kodama, T., Tsai, M.J., Tsai, S.Y. Mol. Endocrinol. (2006) [Pubmed]
  9. The COUP-TF nuclear receptors regulate cell migration in the mammalian basal forebrain. Tripodi, M., Filosa, A., Armentano, M., Studer, M. Development (2004) [Pubmed]
  10. Chicken ovalbumin upstream promoter-transcription factor members repress retinoic acid-induced Cdx1 expression. Béland, M., Lohnes, D. J. Biol. Chem. (2005) [Pubmed]
  11. Coup-TFII is up-regulated in adenovirus type 12 tumorigenic cells and is a repressor of MHC class I transcription. Smirnov, D.A., Hou, S., Liu, X., Claudio, E., Siebenlist, U.K., Ricciardi, R.P. Virology (2001) [Pubmed]
  12. Antagonism of COUP-TF and PPAR alpha/RXR alpha on the activation of the malic enzyme gene promoter: modulation by 9-cis RA. Baes, M., Castelein, H., Desmet, L., Declercq, P.E. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  13. Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors. Jonk, L.J., de Jonge, M.E., Pals, C.E., Wissink, S., Vervaart, J.M., Schoorlemmer, J., Kruijer, W. Mech. Dev. (1994) [Pubmed]
  14. Localization of transcripts of the related nuclear orphan receptors COUP-TF I and ARP-1 in the adult mouse brain. Lopes da Silva, S., Cox, J.J., Jonk, L.J., Kruijer, W., Burbach, J.P. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  15. Spatiotemporal expression patterns of chicken ovalbumin upstream promoter-transcription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalon. Qiu, Y., Cooney, A.J., Kuratani, S., DeMayo, F.J., Tsai, S.Y., Tsai, M.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  16. COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene. Liu, Y., Yang, N., Teng, C.T. Mol. Cell. Biol. (1993) [Pubmed]
  17. Expression of COUP-TFII in metabolic tissues during development. Zhang, P., Bennoun, M., Gogard, C., Bossard, P., Leclerc, I., Kahn, A., Vasseur-Cognet, M. Mech. Dev. (2002) [Pubmed]
  18. Inhibitors of preadipocyte differentiation induce COUP-TF binding to a PPAR/RXR binding sequence. Brodie, A.E., Manning, V.A., Hu, C.Y. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  19. 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. Anderson, G.W., Larson, R.J., Oas, D.R., Sandhofer, C.R., Schwartz, H.L., Mariash, C.N., Oppenheimer, J.H. J. Biol. Chem. (1998) [Pubmed]
  20. Expression screening reveals an orphan receptor chick ovalbumin upstream promoter transcription factor I as a regulator of neurite/substrate-cell contacts and cell aggregation. Connor, H., Nornes, H., Neuman, T. J. Biol. Chem. (1995) [Pubmed]
  21. A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program. Sack, M.N., Disch, D.L., Rockman, H.A., Kelly, D.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  22. The nuclear receptor COUP-TFI represses differentiation of Cajal-Retzius cells. Studer, M., Filosa, A., Rubenstein, J.L. Brain Res. Bull. (2005) [Pubmed]
  23. Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter. Huggins, G.S., Bacani, C.J., Boltax, J., Aikawa, R., Leiden, J.M. J. Biol. Chem. (2001) [Pubmed]
  24. All-trans retinoic acid affects the expression of orphan receptors COUP-TF I and COUP-TF II in the developing neural tube. Brubaker, K., McMillan, M., Neuman, T., Nornes, H.O. Brain Res. Dev. Brain Res. (1996) [Pubmed]
  25. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) regulates cell migration and axogenesis in differentiating P19 embryonal carcinoma cells. Adam, F., Sourisseau, T., Métivier, R., Le Page, Y., Desbois, C., Michel, D., Salbert, G. Mol. Endocrinol. (2000) [Pubmed]
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