Nanog (Gene Nanog)
The NANOG gene (map locus 12p13.31) product, homeobox protein Nanog, is a 305 amino acids long (34.6 kDa), homeodomain motif containing (DNA binding, 95 to 154 region) transcription factor. Two splice variants (Nanog-delta) have been reported with 26 amino acids deleted from the 168 to 183 region, Hart et al. (2004). The sequence from 196 to 240 is enriched with TRP (W) initiated repeat sequences.
Nanog is expressed in undifferentiated cells including fetal gonads (ovary and testis), and embryonic stem (ES) cells. It is also expressed from 14 to 19 weeks of gestation in inner cell mass (ICM) blastocyst cells, morula-stage embryos, epiblast of E6.5 and E7.5 embryos and gonocytes, and long-lived germ cells responsible for gametogenesis. Nanog is expressed in germ-cell tumors of the gonads, testicular embryonic carcinoma, seminoma, and embryonal carcinoma, and CNS germinoma.
Nanog expression in blastocyst inner cellular mass (ICM) cells prevents their differentiation into extra-embryonic endoderm and trophectoderm. In embryonic stem (ES) cells, Nanog blocks bone morphogenic protein-induced mesoderm differentiation via SMAD1. The LIF/STAT3 cytokine pathway can maintain self-renewal in mouse ES cells, but this pathway is not required for renewal of ICM and human ES cells when Nanog is expressed. Nanog induced ES cell self-renewal is LIF/STAT3 pathway independent, Chambers et al. (2003); Mitsui et al. (2003).
Similar to OCT4, Nanog may function as a key regulator for sustaining pluripotency in a dose-dependent manner. Nanog is part of a protein network that functions as a cellular module dedicated to pluripotency, Wang et al. (2006). Members of this network include Dax1, Nac1, Zfp281, and OCT4. Transcription factors Oct-3/4, Nanog, Sox2, and FoxD3 anchor a negative feedback loop to maintain the expression of pluripotent factors at a steady state, Pan G, et al. (2006). Chamber I, et al. (2007) have suggested that Nanog stabilizes embryonic stem cells by resisting or reversing alternative gene states; however it is not essential for somatic (housekeeping) pluripotency. Conversely, Nanog is essential for development of inner cell mass and germ cells.
Nanog, POU5F1/OCT4 and SOX2 are required for propagation of undifferentiated ES cells in culture. These genes function together to establish embryonic stem cell identity, stemness and pluripotency. Nanog, OCT4, and SOX2 co-occupy at least 353 target genes, which include many homeodomain containing transcription factors. Over 90% of the promoter regions bound by OCT4/SOX2 also contained Nanog. Together they create a regulatory circuitry composed of autoregulation and feedforward loops, Boyer, L.A. et al. (2005).
Within the last few years scientists have identified genes that are capable of inducing dedifferentiation of somatic cells into embryonic stem cells called induced pluripotent stem (iPS) cells. The first four transgenes identified include Oct3/4, Sox2, c-Myc, and Klf4, Takahashi K et al. (2006); Wernig et al. (2007). Another transgene set including Nanog, Oct4, Sox2 and LIN28 is also able to induce dedifferentiation of human somatic cells into pluripotent stem cells with a phenotype very similar to that of embryonic stem cells, Yu J. et al. (2007)
Sigma offers antibodies, shRNAs and other products useful for the study of the NANOG Gene.
References:
Boyer, L.A. et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 122: 947-956.
Chambers, I. et al. (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 113: 643-655.
Chambers, I. et al. (2007) Nanog safeguards pluripotency and mediates germline development. Nature. 450: 1230-1234.
Hart, A.H. et al. (2004) Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. Dev Dyn. 230: 187-198.
Mitsui K., et al. (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113: 631-642.
Pan, G. et al. (2006) A negative feedback loop of transcription factors that controls stem cell pluripotency and self-renewal. FASEB J. 20: 1730-1732.
Takahashi, K. and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126: 663-676.
Wernig, M. et al. (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 448: 318-324.
Wang, J. et al. (2006) A protein interaction network for pluripotency of embryonic stem cells. Nature. 444: 364-268.
Yu, J. et al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science. 318: 1917-1920.
Footnote: Gene Data Sources: HGNC, Entrez Gene, UniProt/Swiss-Prot, UniProt/TrEMBL, GDB, OMIM, GeneLoc, Ensembl.
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