Expression of NANOG

Stable Identifier
Reaction [omitted]
Homo sapiens
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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
This event is regulated
Positively by

EPAS1 (HIF2A) enhances expression of NANOG by an unknown mechanism. Expression of EPAS1 is activated by hypoxia via HIF3A.


ZIC3 enhances expression of NANOG (Lim et al. 2007, Lim et al. 2010). In mouse Zic3 binds the Nanog promoter (Lim et al. 2010).

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