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Gene Review

NANOG  -  Nanog homeobox

Homo sapiens

Synonyms: FLJ12581, FLJ40451, Homeobox protein NANOG, Homeobox transcription factor Nanog, hNanog
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Disease relevance of NANOG


High impact information on NANOG

  • We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes [4].
  • Nanog: a new recruit to the embryonic stem cell orchestra [5].
  • Nanog, a homeobox transcription factor, plays a crucial role in the second embryonic cell fate specification following formation of the blastocyst [5].
  • Nanog mRNA is present in pluripotent mouse and human cell lines, and absent from differentiated cells [6].
  • Elevated Nanog expression from transgene constructs is sufficient for clonal expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels [6].

Biological context of NANOG

  • Here we describe the location, genomic organization, and relative ages of all human NANOG pseudogenes, comprising ten processed pseudogenes and one tandem duplicate [7].
  • Indeed, PD98059 prevented Nanog repression induced by ES cell aggregation as well [8].
  • Furthermore, transfection of a constitutive active Mek mutant into ES cells induced Nanog repression and primitive endoderm differentiation [8].
  • Chromatin immunoprecipitation and promoter reporter assays showed that Tcf3 bound to a promoter regulatory region of the Nanog gene and repressed its transcriptional activity in ESC through a Groucho interaction domain-dependent process [9].
  • These data indicate that the Grb2/Mek pathway primarily mediates Nanog gene repression upon ES cell differentiation into primitive endoderm [8].

Anatomical context of NANOG

  • These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal [4].
  • To examine the function of NANOG in primate ES cells, we generated transgenic monkey ES cell lines expressing three- to seven-fold higher levels of NANOG protein compared to wild-type ES cells [10].
  • In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens [1].
  • Taken together, this novel expression pattern of NANOG in goat preimplantation embryos suggests that NANOG could serve as marker of pluripotency in goats and may be useful in derivation and characterization of caprine ESC [11].
  • Human NT2 cells, which differentiate into neurons and astrocytes, initially express and then permanently down-regulate Nanog and Oct-4 (POU5F1) [12].

Associations of NANOG with chemical compounds

  • Of interest, addition of the tyrosine phosphatase inhibitor, sodium vanadate, selectively repressed Nanog transcription without any detectable changes in upstream transcriptional regulators Oct3/4 and Sox2 [8].
  • Developmental expression of pluripotency determining factors in caprine embryos: Novel pattern of NANOG protein localization in the nucleolus [11].
  • All three hESC lines expressed specific markers for non-differentiation (Nanog, stage-specific embryonic antigen-4 [SSEA-4], tumour-related antigen [TRA]-1-60, and TRA-1-81) and were negative for SSEA-1 [13].
  • Co-immunoprecipitation and glutathione S-transferase pulldown experiments confirmed the interaction between Nanog and Sall4 [14].

Regulatory relationships of NANOG

  • A reporter plasmid assay also showed that both variants of nanog modestly repressed transactivation of gata-4, whose expression is proposed to be inhibited by nanog, with comparable potency [15].
  • In this context, p53 induces the differentiation of DNA-damaged ESCs by directly suppressing the expression of Nanog, which is critical for the self-renewal of ESCs [16].
  • NANOG has antisense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding messenger RNAs with sense Alu elements, as well as Pol-III transcribed Alus [17].

Other interactions of NANOG


Analytical, diagnostic and therapeutic context of NANOG


  1. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Hoei-Hansen, C.E., Almstrup, K., Nielsen, J.E., Brask Sonne, S., Graem, N., Skakkebaek, N.E., Leffers, H., Rajpert-De Meyts, E. Histopathology (2005) [Pubmed]
  2. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Clark, A.T., Rodriguez, R.T., Bodnar, M.S., Abeyta, M.J., Cedars, M.I., Turek, P.J., Firpo, M.T., Reijo Pera, R.A. Stem Cells (2004) [Pubmed]
  3. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Ezeh, U.I., Turek, P.J., Reijo, R.A., Clark, A.T. Cancer (2005) [Pubmed]
  4. Core transcriptional regulatory circuitry in human embryonic stem cells. Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S., Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G., Gifford, D.K., Melton, D.A., Jaenisch, R., Young, R.A. Cell (2005) [Pubmed]
  5. Nanog: a new recruit to the embryonic stem cell orchestra. Cavaleri, F., Schöler, H.R. Cell (2003) [Pubmed]
  6. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S., Smith, A. Cell (2003) [Pubmed]
  7. Eleven daughters of NANOG. Booth, H.A., Holland, P.W. Genomics (2004) [Pubmed]
  8. The grb2/mek pathway represses nanog in murine embryonic stem cells. Hamazaki, T., Kehoe, S.M., Nakano, T., Terada, N. Mol. Cell. Biol. (2006) [Pubmed]
  9. Repression of nanog gene transcription by tcf3 limits embryonic stem cell self-renewal. Pereira, L., Yi, F., Merrill, B.J. Mol. Cell. Biol. (2006) [Pubmed]
  10. NANOG maintains self-renewal of primate ES cells in the absence of a feeder layer. Yasuda, S.Y., Tsuneyoshi, N., Sumi, T., Hasegawa, K., Tada, T., Nakatsuji, N., Suemori, H. Genes Cells (2006) [Pubmed]
  11. Developmental expression of pluripotency determining factors in caprine embryos: Novel pattern of NANOG protein localization in the nucleolus. He, S., Pant, D., Schiffmacher, A., Bischoff, S., Melican, D., Gavin, W., Keefer, C. Mol. Reprod. Dev. (2006) [Pubmed]
  12. Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. Deb-Rinker, P., Ly, D., Jezierski, A., Sikorska, M., Walker, P.R. J. Biol. Chem. (2005) [Pubmed]
  13. Derivation and characterization of three new Spanish human embryonic stem cell lines (VAL -3 -4 -5) on human feeder and in serum-free conditions. Valbuena, D., Gal??n, A., S??nchez, E., Poo, M.E., G??mez, E., S??nchez-Luengo, S., Melguizo, D., Garc??a, A., Ruiz, V., Moreno, R., Pellicer, A., Sim??n, C. Reprod. Biomed. Online (2006) [Pubmed]
  14. Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. Wu, Q., Chen, X., Zhang, J., Loh, Y.H., Low, T.Y., Zhang, W., Zhang, W., Sze, S.K., Lim, B., Ng, H.H. J. Biol. Chem. (2006) [Pubmed]
  15. Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog. Kim, J.S., Kim, J., Kim, B.S., Chung, H.Y., Lee, Y.Y., Park, C.S., Lee, Y.S., Lee, Y.H., Chung, I.Y. Exp. Mol. Med. (2005) [Pubmed]
  16. A new role for p53 in maintaining genetic stability in embryonic stem cells. Xu, Y. Cell Cycle (2005) [Pubmed]
  17. A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs WikiGenes. Publication
  18. Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors. Korkola, J.E., Houldsworth, J., Chadalavada, R.S., Olshen, A.B., Dobrzynski, D., Reuter, V.E., Bosl, G.J., Chaganti, R.S. Cancer Res. (2006) [Pubmed]
  19. Research of cardiomyocyte precursors in adult rat heart. Bellafiore, M., Sivverini, G., Cappello, F., David, S., Palma, A., Farina, F., Zummo, G. Tissue & cell (2006) [Pubmed]
  20. Evolution of the NANOG pseudogene family in the human and chimpanzee genomes. Fairbanks, D.J., Maughan, P.J. BMC Evol. Biol. (2006) [Pubmed]
  21. The stem cell pluripotency factor NANOG activates transcription with two unusually potent subdomains at its C terminus. Pan, G., Pei, D. J. Biol. Chem. (2005) [Pubmed]
  22. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Darr, H., Mayshar, Y., Benvenisty, N. Development (2006) [Pubmed]
  23. Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers. Hoei-Hansen, C.E., Carlsen, E., Jorgensen, N., Leffers, H., Skakkebaek, N.E., Rajpert-De Meyts, E. Hum. Reprod. (2007) [Pubmed]
  24. The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Hart, A.H., Hartley, L., Parker, K., Ibrahim, M., Looijenga, L.H., Pauchnik, M., Chow, C.W., Robb, L. Cancer (2005) [Pubmed]
  25. Spatial organization of embryonic stem cell responsiveness to autocrine gp130 ligands reveals an autoregulatory stem cell niche. Davey, R.E., Zandstra, P.W. Stem Cells (2006) [Pubmed]
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