Germ cell nuclear factor explained

The germ cell nuclear factor (GCNF), also known as RTR (retinoid receptor-related testis-associated receptor) or NR6A1 (nuclear receptor subfamily 6, group A, member 1), is a protein that in humans is encoded by the NR6A1 gene.^{[1] [2]} GCNF is a member of the nuclear receptor family of intracellular transcription factors .

In adults, GCNH is expressed mainly in the germ cells of gonads and is involved in the regulation of embryogenesis and germ cell differentiation.^[3]

Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. The gene expresses three alternatively spliced transcript variants.^[4]

In cells undergoing homologous recombination during meiosis, DNA intermediates are processed as an essential step in the exchange of information between parental homologous chromosomes. In eukaryotes the RTR complex, which consists of a type IA topoisomerase, a RecQ helicase and the structural protein RMI1, is employed in processing DNA recombination intermediates.^[5]

Further reading

• Greschik H, Schüle R . Germ cell nuclear factor: an orphan receptor with unexpected properties . Journal of Molecular Medicine . 76 . 12 . 800–10 . 1999 . 9846950 . 10.1007/s001090050284 . 9368668 .
• Hirose T, O'Brien DA, Jetten AM . RTR: a new member of the nuclear receptor superfamily that is highly expressed in murine testis . Gene . 152 . 2 . 247–51 . Jan 1995 . 7835709 . 10.1016/0378-1119(94)00656-D .
• Yan ZH, Medvedev A, Hirose T, Gotoh H, Jetten AM . Characterization of the response element and DNA binding properties of the nuclear orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor . The Journal of Biological Chemistry . 272 . 16 . 10565–72 . Apr 1997 . 9099702 . 10.1074/jbc.272.16.10565 . free .
• Kapelle M, Krätzschmar J, Husemann M, Schleuning WD . cDNA cloning of two closely related forms of human germ cell nuclear factor (GCNF) . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1352 . 1 . 13–7 . May 1997 . 9177477 . 10.1016/s0167-4781(97)00043-2 .
• Agoulnik IY, Cho Y, Niederberger C, Kieback DG, Cooney AJ . Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF . FEBS Letters . 424 . 1–2 . 73–8 . Mar 1998 . 9537518 . 10.1016/S0014-5793(98)00142-2 . 26848550 . free . 1998FEBSL.424...73A .
• Greschik H, Wurtz JM, Hublitz P, Köhler F, Moras D, Schüle R . Characterization of the DNA-binding and dimerization properties of the nuclear orphan receptor germ cell nuclear factor . Molecular and Cellular Biology . 19 . 1 . 690–703 . Jan 1999 . 9858592 . 83926 . 10.1128/mcb.19.1.690.
• Schmitz TP, Süsens U, Borgmeyer U . DNA binding, protein interaction and differential expression of the human germ cell nuclear factor . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1446 . 3 . 173–80 . Sep 1999 . 10524192 . 10.1016/s0167-4781(99)00079-2 .
• Yan Z, Jetten AM . Characterization of the repressor function of the nuclear orphan receptor retinoid receptor-related testis-associated receptor/germ cell nuclear factor . The Journal of Biological Chemistry . 275 . 45 . 35077–85 . Nov 2000 . 10940306 . 10.1074/jbc.M005566200 . free .
• Süsens U, Borgmeyer U . Genomic structure of the gene for mouse germ-cell nuclear factor (GCNF). II. Comparison with the genomic structure of the human GCNF gene . Genome Biology . 2 . 5 . RESEARCH0017 . 2001 . 11387038 . 32189 . 10.1186/gb-2001-2-5-research0017 . free .
• Mehta DV, Kim YS, Dixon D, Jetten AM . Characterization of the expression of the retinoid-related, testis-associated receptor (RTR) in trophoblasts . Placenta . 23 . 4 . 281–7 . Apr 2002 . 11969338 . 10.1053/plac.2001.0779 .
• Yan Z, Kim YS, Jetten AM . RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor . The Journal of Biological Chemistry . 277 . 35 . 32379–88 . Aug 2002 . 12080054 . 10.1074/jbc.M203475200 . free .
• Lan ZJ, Chung AC, Xu X, DeMayo FJ, Cooney AJ . The embryonic function of germ cell nuclear factor is dependent on the DNA binding domain . The Journal of Biological Chemistry . 277 . 52 . 50660–7 . Dec 2002 . 12381721 . 10.1074/jbc.M209586200 . free .
• Yang G, Zhang YL, Buchold GM, Jetten AM, O'Brien DA . Analysis of germ cell nuclear factor transcripts and protein expression during spermatogenesis . Biology of Reproduction . 68 . 5 . 1620–30 . May 2003 . 12606326 . 10.1095/biolreprod.102.012013 . free .
• Rajkovic M, Middendorff R, Wetzel MG, Frkovic D, Damerow S, Seitz HJ, Weitzel JM . Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated activation of the testis-specific promoter of human mitochondrial glycerol-3-phosphate dehydrogenase . The Journal of Biological Chemistry . 279 . 50 . 52493–9 . Dec 2004 . 15456763 . 10.1074/jbc.M404467200 . free .

Notes and References

1. Lei W, Hirose T, Zhang LX, Adachi H, Spinella MJ, Dmitrovsky E, Jetten AM . 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 . Journal of Molecular Endocrinology . 18 . 2 . 167–76 . Apr 1997 . 9134503 . 10.1677/jme.0.0180167 .
2. Süsens U, Borgmeyer U . Characterization of the human germ cell nuclear factor gene . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1309 . 3 . 179–82 . Dec 1996 . 8982251 . 10.1016/s0167-4781(96)00157-1 .
3. Zechel C . The germ cell nuclear factor (GCNF) . Molecular Reproduction and Development . 72 . 4 . 550–6 . Dec 2005 . 16155958 . 10.1002/mrd.20377 . 39315293 . free .
4. Web site: Entrez Gene: NR6A1 nuclear receptor subfamily 6, group A, member 1.
5. Knoll A, Schröpfer S, Puchta H . The RTR complex as caretaker of genome stability and its unique meiotic function in plants . Front Plant Sci . 5 . 33 . 2014 . 24575106 . 3921566 . 10.3389/fpls.2014.00033 . free.