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Gene Review

Nr6a1  -  nuclear receptor subfamily 6, group A,...

Mus musculus

Synonyms: 1700113M01Rik, GCNF, Gcnf, Germ cell nuclear factor, NCNF, ...
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Disease relevance of Nr6a1

  • To test the prediction that GCNF is additionally required for neuronal differentiation, we used the mouse embryonal carcinoma cell line PCC7-Mz1, which represents an advantageous model to study neuronal cells from the stage of fate choice until the acquirement of functional competence [1].

High impact information on Nr6a1


Biological context of Nr6a1

  • GCNF therefore defines a novel nuclear receptor-signaling pathway that may regulate a subset of genes involved in the terminal differentiation process of spermatogenesis, exemplified by the protamines [4].
  • Furthermore, we have previously identified a sequence to which GCNF can bind, which consists of a direct repeat of the core halfsite AGGTCA with zero base pairs spacing the repeats (DRO) [5].
  • GCNF binds as a homodimer to direct repeat response elements of the consensus half-site sequence, AGGTCA, with 0 bp spacing (DR0) [4].
  • A boundary for histone acetylation allows distinct expression patterns of the Ad4BP/SF-1 and GCNF loci in adrenal cortex cells [6].
  • GCNF overexpression in embryonal cells represses Oct4 gene and transgene activities, and we establish a link to transcriptional corepressors mediating repression by GCNF [7].

Anatomical context of Nr6a1

  • Germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily, which is expressed in the adult predominantly in the male and female germ cells [4].
  • Furthermore, by using antibodies directed against GCNF, we detect endogenous GCNF in testis nuclear extracts and elutriated round spermatid nuclear extracts in Western blots [5].
  • This evidence supports the hypothesis that GCNF mediates a novel signaling pathway, two targets of which may be the Prm1 and Prm2 genes in spermatids [5].
  • Immunohistochemical analysis using an ELP-specific antibody showed that expression was very restricted within the testis to the postmeiotic germ cells, and in the ovary to interstitial/luteal cells, cell-types known to express GCNF and SF-1, respectively [8].
  • Our studies suggest that GCNF is critical in repressing Oct4 gene activity as pluripotent stem cells differentiate and in confining Oct4 expression to the germline [7].

Associations of Nr6a1 with chemical compounds


Regulatory relationships of Nr6a1


Other interactions of Nr6a1

  • Within this YAC, Ftz-F1 is centrally located and flanked by genes encoding a second orphan nuclear receptor, germ cell nuclear factor, and proteasome (prosome, macropain) subunit beta type 7 [13].
  • The mouse protamine 1 and 2 (Prm1 and Prm2) genes therefore are potential target genes for GCNF regulation [5].
  • Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup-tf1, and GCNF was stimulated by GABPalpha knockdown [14].
  • Interestingly, the tailbud of GCNF(-/-) embryos develops ectopically outside the yolk sac [15].
  • It implies that some androgen-regulated gene expressions located at the corpus principal cells might be controlled by GCNF [9].

Analytical, diagnostic and therapeutic context of Nr6a1


  1. The expression level of the orphan nuclear receptor GCNF (germ cell nuclear factor) is critical for neuronal differentiation. Sattler, U., Samochocki, M., Maelicke, A., Zechel, C. Mol. Endocrinol. (2004) [Pubmed]
  2. GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility. Lan, Z.J., Gu, P., Xu, X., Jackson, K.J., DeMayo, F.J., O'Malley, B.W., Cooney, A.J. EMBO J. (2003) [Pubmed]
  3. Orphan nuclear receptor GCNF is required for the repression of pluripotency genes during retinoic acid-induced embryonic stem cell differentiation. Gu, P., LeMenuet, D., Chung, A.C., Mancini, M., Wheeler, D.A., Cooney, A.J. Mol. Cell. Biol. (2005) [Pubmed]
  4. Reciprocal regulation of the mouse protamine genes by the orphan nuclear receptor germ cell nuclear factor and CREMtau. Hummelke, G.C., Cooney, A.J. Mol. Reprod. Dev. (2004) [Pubmed]
  5. Mouse protamine genes are candidate targets for the novel orphan nuclear receptor, germ cell nuclear factor. Hummelke, G.C., Meistrich, M.L., Cooney, A.J. Mol. Reprod. Dev. (1998) [Pubmed]
  6. A boundary for histone acetylation allows distinct expression patterns of the Ad4BP/SF-1 and GCNF loci in adrenal cortex cells. Ishihara, S.L., Morohashi, K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  7. Mouse germline restriction of Oct4 expression by germ cell nuclear factor. Fuhrmann, G., Chung, A.C., Jackson, K.J., Hummelke, G., Baniahmad, A., Sutter, J., Sylvester, I., Schöler, H.R., Cooney, A.J. Dev. Cell (2001) [Pubmed]
  8. Structure and expression of the mouse gene encoding the endozepine-like peptide from haploid male germ cells. Valentin, M., Balvers, M., Pusch, W., Weinbauer, G.F., Knudsen, J., Ivell, R. Eur. J. Biochem. (2000) [Pubmed]
  9. Androgen down-regulated and region-specific expression of germ cell nuclear factor in mouse epididymis. Hu, Y., Zhou, Z., Xu, C., Shang, Q., Zhang, Y.D., Zhang, Y.L. Endocrinology (2003) [Pubmed]
  10. Dimeric binding of the mouse germ cell nuclear factor. Borgmeyer, U. Eur. J. Biochem. (1997) [Pubmed]
  11. The murine nuclear orphan receptor GCNF is expressed in the XY body of primary spermatocytes. Bauer, U.M., Schneider-Hirsch, S., Reinhardt, S., Benavente, R., Maelicke, A. FEBS Lett. (1998) [Pubmed]
  12. A binding site for germ cell nuclear factor within c-mos regulatory sequences. Zilz, A., Cooper, G.M. Mol. Reprod. Dev. (2004) [Pubmed]
  13. A FTZ-F1-containing yeast artificial chromosome recapitulates expression of steroidogenic factor 1 in vivo. Karpova, T., Presley, J., Manimaran, R.R., Scherrer, S.P., Tejada, L., Peterson, K.R., Heckert, L.L. Mol. Endocrinol. (2005) [Pubmed]
  14. GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells. Kinoshita, K., Ura, H., Akagi, T., Usuda, M., Koide, H., Yokota, T. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  15. Loss of orphan receptor germ cell nuclear factor function results in ectopic development of the tail bud and a novel posterior truncation. Chung, A.C., Katz, D., Pereira, F.A., Jackson, K.J., DeMayo, F.J., Cooney, A.J., O'Malley, B.W. Mol. Cell. Biol. (2001) [Pubmed]
  16. Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor. Katz, D., Niederberger, C., Slaughter, G.R., Cooney, A.J. Endocrinology (1997) [Pubmed]
  17. Spatial and temporal expression of germ cell nuclear factor in murine epididymis. Zhou, Z.Y., Xu, C., Guo, Q.S., Hu, Y.X., Zhang, Y.L., Wang, Y.F. Asian J. Androl. (2004) [Pubmed]
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