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Gene Review

NR6A1  -  nuclear receptor subfamily 6, group A,...

Homo sapiens

Synonyms: CT150, GCNF, GCNF1, Germ cell nuclear factor, NR61, ...
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Disease relevance of NR6A1


High impact information on NR6A1

  • Here we show that the orphan nuclear receptor GCNF initiates Oct4 repression and DNA methylation by the differential recruitment of MBD (methylated CpG binding domain) factors to the promoter [6].
  • GCNF initiates the repression and epigenetic modification of Oct4 gene during ES cell differentiation [6].
  • During development, GCNF exhibits a restricted brain-specific expression pattern, whereas GCNF expression in the adult is germ cell specific [7].
  • No natural GCNF target gene has yet been identified, but recent data demonstrate specific and high-affinity binding of GCNF either to the direct repeat DNA element AGGTCAAGGTCA (DR0) or to extended half-sites, such as TCAAGGTCA [7].
  • Characterization of the DNA-binding and dimerization properties of the nuclear orphan receptor germ cell nuclear factor [7].

Chemical compound and disease context of NR6A1


Biological context of NR6A1


Anatomical context of NR6A1

  • We report the cloning of a cDNA encoding a new variant of human GCNF from human testis and its expression analysis [11].
  • GCNF/RTR was also highly expressed in embryonic stem cells and embryonal carcinoma cells but repressed in its differentiated derivatives [1].
  • These results suggest the possibility of cross-talk between RTR and ERR alpha receptor signalling pathways in trophoblasts [2].
  • Northern blot analysis using RNA from different testicular cell types showed that RTR mRNA is not expressed in early germ cells or Sertoli cells but is most abundant in round spermatids [12].
  • In addition, full neuronal differentiation is not observed in the midbrain region of GCNF(-/-) embryos [13].

Associations of NR6A1 with chemical compounds

  • Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated activation of the testis-specific promoter of human mitochondrial glycerol-3-phosphate dehydrogenase [10].
  • Due to the lack of a conserved transcriptional activation function 2 core motif (AF-2 AD core) in the helix 12 region of the GCNF LBD, it has been suggested that GCNF functions as a repressor of transcription [14].
  • In trophoblasts, RTR was co-expressed with the estrogen-related receptors ERR alpha and ERR beta [2].
  • (ii) SF-1, which controls the fate of two steroid hormone-producing organs, adrenals and gonads, is descended from the invertebrate Ftz-F1 gene, and its only known paralogue is GCNF-1 [15].
  • This review will discuss 18 supplementation studies conducted in ESRF and 6 in RTR investigating the effects of nutritional therapy to lower homocysteine [4].

Physical interactions of NR6A1


Other interactions of NR6A1

  • Our results demonstrate that RTR can function as an active transcriptional repressor and that this repression can be mediated through interactions with the co-repressor N-CoR [9].
  • GCNF has been shown to be a repressor of the protamine and Oct4 genes [16].
  • Nuclear orphan receptors oestrogen receptor-related receptor alpha (ERRalpha) and germ cell nuclear factor (GCNF) are expressed to significant levels in MDA-MB 231 cells [17].

Analytical, diagnostic and therapeutic context of NR6A1


  1. Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation. Lei, W., Hirose, T., Zhang, L.X., Adachi, H., Spinella, M.J., Dmitrovsky, E., Jetten, A.M. J. Mol. Endocrinol. (1997) [Pubmed]
  2. Characterization of the expression of the retinoid-related, testis-associated receptor (RTR) in trophoblasts. Mehta, D.V., Kim, Y.S., Dixon, D., Jetten, A.M. Placenta (2002) [Pubmed]
  3. Germ Cell Nuclear Factor Is a Repressor of CRIPTO-1 and CRIPTO-3. Hentschke, M., Kurth, I., Borgmeyer, U., H??bner, C.A. J. Biol. Chem. (2006) [Pubmed]
  4. Homocysteine-lowering therapy in renal disease. Austen, S.K., Coombes, J.S., Fassett, R.G. Clin. Nephrol. (2003) [Pubmed]
  5. Hypertension in renal transplantation: donor and recipient risk factors. Ducloux, D., Motte, G., Kribs, M., Abdelfatah, A.B., Bresson-Vautrin, C., Rebibou, J.M., Chalopin, J.M. Clin. Nephrol. (2002) [Pubmed]
  6. Differential Recruitment of Methylated CpG Binding Domains by the Orphan Receptor GCNF Initiates the Repression and Silencing of Oct4 Expression. Gu, P., Le Menuet, D., Chung, A.C., Cooney, A.J. Mol. Cell. Biol. (2006) [Pubmed]
  7. Characterization of the DNA-binding and dimerization properties of the nuclear orphan receptor germ cell nuclear factor. Greschik, H., Wurtz, J.M., Hublitz, P., Köhler, F., Moras, D., Schüle, R. Mol. Cell. Biol. (1999) [Pubmed]
  8. RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor. Yan, Z., Kim, Y.S., Jetten, A.M. J. Biol. Chem. (2002) [Pubmed]
  9. Characterization of the repressor function of the nuclear orphan receptor retinoid receptor-related testis-associated receptor/germ cell nuclear factor. Yan, Z., Jetten, A.M. J. Biol. Chem. (2000) [Pubmed]
  10. Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated activation of the testis-specific promoter of human mitochondrial glycerol-3-phosphate dehydrogenase. Rajkovic, M., Middendorff, R., Wetzel, M.G., Frkovic, D., Damerow, S., Seitz, H.J., Weitzel, J.M. J. Biol. Chem. (2004) [Pubmed]
  11. Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF. Agoulnik, I.Y., Cho, Y., Niederberger, C., Kieback, D.G., Cooney, A.J. FEBS Lett. (1998) [Pubmed]
  12. RTR: a new member of the nuclear receptor superfamily that is highly expressed in murine testis. Hirose, T., O'Brien, D.A., Jetten, A.M. Gene (1995) [Pubmed]
  13. Loss of orphan nuclear receptor GCNF function disrupts forebrain development and the establishment of the isthmic organizer. Chung, A.C., Xu, X., Niederreither, K.A., Cooney, A.J. Dev. Biol. (2006) [Pubmed]
  14. Germ cell nuclear factor: an orphan receptor with unexpected properties. Greschik, H., Schüle, R. J. Mol. Med. (1998) [Pubmed]
  15. The one-to-four rule and paralogues of sex-determining genes. Ohno, S. Cell. Mol. Life Sci. (1999) [Pubmed]
  16. Germ cell nuclear factor is a transcriptional repressor essential for embryonic development. Hummelke, G.C., Cooney, A.J. Front. Biosci. (2001) [Pubmed]
  17. Transcriptional activation of the oxytocin promoter by oestrogens uses a novel non-classical mechanism of oestrogen receptor action. Koohi, M.K., Ivell, R., Walther, N. J. Neuroendocrinol. (2005) [Pubmed]
  18. DNA binding, protein interaction and differential expression of the human germ cell nuclear factor. Schmitz, T.P., Süsens, U., Borgmeyer, U. Biochim. Biophys. Acta (1999) [Pubmed]
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