Reactome | Expression of NANOG

Expression of NANOG

Stable Identifier

R-HSA-452838

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

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The NANOG gene is transcribed to yield mRNA and the mRNA is translated to yield protein (Chambers et al. 2003, Hart et al. 2004, Hatano et al. 2005, Hyslop et al. 2005, Li et al. 2006). NANOG protein is not detected in oocytes or early cleavage-stage embryos, but is seen later in some but not all nuclei of the inner cell mass of blastocysts (Cauffman et al. 2009). KLF4, PBX1, POU5F1 (OCT4), SOX2, NANOG, and SMAD2 bind the promoter of the NANOG gene and enhance transcription (Boyer et al. 2005, Rodda et al. 2005, Kuroda et al. 2005, Babaie et al. 2007, Assou et al. 2007, Greber et al. 2007, Vallier et al. 2009, Brown et al. 2011). Activation-induced cytidine deaminase (AID) binds the methylated NANOG promoter and demethylates it (Bhutani et al. 2009). Hypoxia acts via HIF3A and EPAS1 (HIF2A) to enhance expression of NANOG (Forristal et al. 2010). In mouse Nanog negatively regulates its own expression and this may account for the heterogeneous expression observed in cells of the inner cell mass (Fidalgo et al. 2012, Navarro et al. 2012). In human embryonic stem cells NANOG has been observed to be expressed monoallelically in the early pre-implantation embryo then expression becomes biallelic (Miyanari and Torres-Padilla 2012), however this is controversial because expreiments in mouse embryonic stem cells have shown biallelic expression (Faddah et al. 2013, Filipczyk et al. 2013). POU5F1 and SOX2 bind adjacent sites at the promoter and form a heterodimer on the DNA. In mice KLF4 interacts with POU5F1 and SOX2.

Literature References

PubMed ID	Title	Journal	Year
23827708	Single-cell analysis reveals that expression of nanog is biallelic and equally variable as that of other pluripotency factors in mouse ESCs Faddah, DA, Wang, H, Cheng, AW, Katz, Y, Buganim, Y, Jaenisch, R	Cell Stem Cell	2013
15983365	Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages Hyslop, L, Stojkovic, M, Armstrong, L, Walter, T, Stojkovic, P, Przyborski, S, Herbert, M, Murdoch, A, Strachan, T, Lako, M	Stem Cells	2005
23827706	Biallelic expression of nanog protein in mouse embryonic stem cells Filipczyk, A, Gkatzis, K, Fu, J, Hoppe, PS, Lickert, H, Anastassiadis, K, Schroeder, T	Cell Stem Cell	2013
17506876	Silencing of core transcription factors in human EC cells highlights the importance of autocrine FGF signaling for self-renewal Greber, B, Lehrach, H, Adjaye, J	BMC Dev. Biol.	2007
12787505	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
23178592	OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells Navarro, P, Festuccia, N, Colby, D, Gagliardi, A, Mullin, NP, Zhang, W, Karwacki-Neisius, V, Osorno, R, Kelly, D, Robertson, M, Chambers, I	EMBO J.	2012
15582778	Pluripotential competence of cells associated with Nanog activity Hatano, SY, Tada, M, Kimura, H, Yamaguchi, S, Kono, T, Nakano, T, Suemori, H, Nakatsuji, N, Tada, T	Mech Dev	2005
20027182	Reprogramming towards pluripotency requires AID-dependent DNA demethylation Bhutani, N, Brady, JJ, Damian, M, Sacco, A, Corbel, SY, Blau, HM	Nature	2009
15108323	Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human Hart, AH, Hartley, L, Ibrahim, M, Robb, L	Dev Dyn	2004
17204602	A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas Assou, S, Le Carrour, T, Tondeur, S, Ström, S, Gabelle, A, Marty, S, Nadal, L, Pantesco, V, Réme, T, Hugnot, JP, Gasca, S, Hovatta, O, Hamamah, S, Klein, B, De Vos, J	Stem Cells	2007
17068183	Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells Babaie, Y, Herwig, R, Greber, B, Brink, TC, Wruck, W, Groth, D, Lehrach, H, Burdon, T, Adjaye, J	Stem Cells	2007
19604364	In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach Chavez, L, Bais, AS, Vingron, M, Lehrach, H, Adjaye, J, Herwig, R	BMC Genomics	2009
19755485	Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions Forristal, CE, Wright, KL, Hanley, NA, Oreffo, RO, Houghton, FD	Reproduction	2010
21630377	Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors Brown, S, Teo, A, Pauklin, S, Hannan, N, Cho, CH, Lim, B, Vardy, L, Dunn, NR, Trotter, M, Pedersen, R, Vallier, L	Stem Cells	2011
19688839	Signaling pathways controlling pluripotency and early cell fate decisions of human induced pluripotent stem cells Vallier, L, Touboul, T, Brown, S, Cho, C, Bilican, B, Alexander, M, Cedervall, J, Chandran, S, Ahrlund-Richter, L, Weber, A, Pedersen, RA	Stem Cells	2009
15860457	Transcriptional regulation of nanog by OCT4 and SOX2 Rodda, DJ, Chew, JL, Lim, LH, Loh, YH, Wang, B, Ng, HH, Robson, P	J Biol Chem	2005
16153702	Core transcriptional regulatory circuitry in human embryonic stem cells Boyer, LA, Lee, TI, Cole, MF, Johnstone, SE, Levine, SS, Zucker, JP, Guenther, MG, Kumar, RM, Murray, HL, Jenner, RG, Gifford, DK, Melton, DA, Jaenisch, R, Young, RA	Cell	2005
18824471	Markers that define stemness in ESC are unable to identify the totipotent cells in human preimplantation embryos Cauffman, G, De Rycke, M, Sermon, K, Liebaers, I, Van de Velde, H	Hum Reprod	2009
15743839	Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression Kuroda, T, Tada, M, Kubota, H, Kimura, H, Hatano, SY, Suemori, H, Nakatsuji, N, Tada, T	Mol Cell Biol	2005
22988117	Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming Fidalgo, M, Faiola, F, Pereira, CF, Ding, J, Saunders, A, Gingold, J, Schaniel, C, Lemischka, IR, Silva, JC, Wang, J	Proc. Natl. Acad. Sci. U.S.A.	2012
22327294	Control of ground-state pluripotency by allelic regulation of Nanog Miyanari, Y, Torres-Padilla, ME	Nature	2012