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Gene Review

Sox2  -  SRY (sex determining region Y)-box 2

Mus musculus

Synonyms: Sox-2, Transcription factor SOX-2, lcc, ysb
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Disease relevance of Sox2

  • Whether disturbance of the regulation of Sox2 and Cdx genes may be of importance to the biological behavior of gastric cancers should therefore be clarified in future studies [1].
  • Sox-2 is also highly expressed in F9 embryonal carcinoma cells, but becomes undetectable following differentiation of these cells [2].
  • Sox2 directly associates with Chd7, which is linked to CHARGE syndrome [3].

High impact information on Sox2

  • Retinal progenitor cells with conditionally ablated Sox2 lose competence to both proliferate and terminally differentiate [4].
  • The transcription factor SOX2 has also been implicated in the regulation of Fgf4 expression [5].
  • Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers [6].
  • Although lens induction occurred in the mutant, as indicated by Sox2 up-regulation in the surface ectoderm, further development of the lens was arrested [7].
  • Sox-2 represses Oct-4 mediated activation of i-opn by way of a canonical Sox element that is located close to the PORE [8].

Biological context of Sox2


Anatomical context of Sox2


Associations of Sox2 with chemical compounds


Physical interactions of Sox2


Regulatory relationships of Sox2

  • By contrast, SOX2 was a poor activator of Fgf-3 transcription, and when Sox2 was coexpressed with Gata4, it negatively modulated the strong activation mediated by GATA-4 [20].
  • In addition, we employed two experimental approaches to demonstrate that Sox-2 regulates the transcription of the FGF-4 gene in EC cells [21].
  • We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2 [22].
  • By contrast, the abnormal foregut of Nkx2.1-null embryos expresses elevated Sox2 and p63, suggesting reciprocal regulation of Sox2 and Nkx2.1 during early dorsal/ventral foregut patterning [23].

Other interactions of Sox2

  • These are always characterized by overlapping expression of Sox2/3 and Pax6 [13].
  • Whole mount in situ hybridisation was used to study the embryonic expression of the mouse HMG box-containing genes Sox1, Sox2 and Sox3 between 6.5 and 9.0 days post coitum (dpc) [24].
  • Sox2 and Sox3 are expressed in the epiblast and extraembryonic ectoderm of the egg cylinder, becoming restricted to the prospective neural plate and chorion at the onset of gastrulation [24].
  • Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal [25].
  • In contrast to the early embryonic lethality observed in Sox2-null mice, Sox15-null ES cells and mice were grossly normal [11].
  • Sox2 associates directly with Exportin 4 and with Chd7 [26] [3].

Analytical, diagnostic and therapeutic context of Sox2

  • We have used gene targeting to inactivate Sox2, examining the phenotypic consequences in mutant embryos and in chimeras in which the epiblast is rescued with wild-type ES cells [5].
  • Survival of the injected ESCs was confirmed by the real-time polymerase chain reaction analysis of stemness genes such as Oct4, Sox2, and FGF4 [27].
  • We report a direct genetic and functional comparison of molecularly defined and clonally related populations of neural SCs (NSCs) and embryonic SCs (ESCs), using the Sox2 promoter for isolation of purified populations by fluorescence-activated cell sorting [28].
  • By RT-PCR, we detected the presence of multiple Sox family members in both the developing pancreas and mature islets and then focused on two factors, Sox2 and Sox4 [29].
  • We demonstrate that these cells express other markers of the sensory lineage, such as Sox2, and when placed in dissociated cell culture differentiate as hair cells and supporting cells [30].


  1. Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia. Tatematsu, M., Tsukamoto, T., Inada, K. Cancer Sci. (2003) [Pubmed]
  2. Isolation, characterization, and differential expression of the murine Sox-2 promoter. Wiebe, M.S., Wilder, P.J., Kelly, D., Rizzino, A. Gene (2000) [Pubmed]
  3. Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes. Engelen, E., Akinci, U., Bryne, J.C., Hou, J., Gontan, C., Moen, M., Szumska, D., Kockx, C., van Ijcken, W., Dekkers, D.H., Demmers, J., Rijkers, E.J., Bhattacharya, S., Philipsen, S., Pevny, L.H., Grosveld, F.G., Rottier, R.J., Lenhard, B., Poot, R.A. Nat. Genet. (2011) [Pubmed]
  4. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Taranova, O.V., Magness, S.T., Fagan, B.M., Wu, Y., Surzenko, N., Hutton, S.R., Pevny, L.H. Genes Dev. (2006) [Pubmed]
  5. Multipotent cell lineages in early mouse development depend on SOX2 function. Avilion, A.A., Nicolis, S.K., Pevny, L.H., Perez, L., Vivian, N., Lovell-Badge, R. Genes Dev. (2003) [Pubmed]
  6. Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Reményi, A., Lins, K., Nissen, L.J., Reinbold, R., Schöler, H.R., Wilmanns, M. Genes Dev. (2003) [Pubmed]
  7. Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Ashery-Padan, R., Marquardt, T., Zhou, X., Gruss, P. Genes Dev. (2000) [Pubmed]
  8. New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Botquin, V., Hess, H., Fuhrmann, G., Anastassiadis, C., Gross, M.K., Vriend, G., Schöler, H.R. Genes Dev. (1998) [Pubmed]
  9. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Yuan, H., Corbi, N., Basilico, C., Dailey, L. Genes Dev. (1995) [Pubmed]
  10. Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. Catena, R., Tiveron, C., Ronchi, A., Porta, S., Ferri, A., Tatangelo, L., Cavallaro, M., Favaro, R., Ottolenghi, S., Reinbold, R., Schöler, H., Nicolis, S.K. J. Biol. Chem. (2004) [Pubmed]
  11. Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells. Maruyama, M., Ichisaka, T., Nakagawa, M., Yamanaka, S. J. Biol. Chem. (2005) [Pubmed]
  12. Sox2 is important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation. Gontan, C., de Munck, A., Vermeij, M., Grosveld, F., Tibboel, D., Rottier, R. Dev. Biol. (2008) [Pubmed]
  13. Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Kamachi, Y., Uchikawa, M., Collignon, J., Lovell-Badge, R., Kondoh, H. Development (1998) [Pubmed]
  14. Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. Okumura-Nakanishi, S., Saito, M., Niwa, H., Ishikawa, F. J. Biol. Chem. (2005) [Pubmed]
  15. Histone arginine methylation regulates pluripotency in the early mouse embryo. Torres-Padilla, M.E., Parfitt, D.E., Kouzarides, T., Zernicka-Goetz, M. Nature (2007) [Pubmed]
  16. The Sox2 Regulatory Region 2 Functions as a Neural Stem Cell-specific Enhancer in the Telencephalon. Miyagi, S., Nishimoto, M., Saito, T., Ninomiya, M., Sawamoto, K., Okano, H., Muramatsu, M., Oguro, H., Iwama, A., Okuda, A. J. Biol. Chem. (2006) [Pubmed]
  17. Role of Sox2 in the development of the mouse neocortex. Bani-Yaghoub, M., Tremblay, R.G., Lei, J.X., Zhang, D., Zurakowski, B., Sandhu, J.K., Smith, B., Ribecco-Lutkiewicz, M., Kennedy, J., Walker, P.R., Sikorska, M. Dev. Biol. (2006) [Pubmed]
  18. Inhibition of DNA binding of Sox2 by the SUMO conjugation. Tsuruzoe, S., Ishihara, K., Uchimura, Y., Watanabe, S., Sekita, Y., Aoto, T., Saitoh, H., Yuasa, Y., Niwa, H., Kawasuji, M., Baba, H., Nakao, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  19. The co-activator p300 associates physically with and can mediate the action of the distal enhancer of the FGF-4 gene. Nowling, T., Bernadt, C., Johnson, L., Desler, M., Rizzino, A. J. Biol. Chem. (2003) [Pubmed]
  20. SOX7 and GATA-4 are competitive activators of Fgf-3 transcription. Murakami, A., Shen, H., Ishida, S., Dickson, C. J. Biol. Chem. (2004) [Pubmed]
  21. Role of the transcription factor Sox-2 in the expression of the FGF-4 gene in embryonal carcinoma cells. Johnson, L.R., Lamb, K.A., Gao, Q., Nowling, T.K., Rizzino, A. Mol. Reprod. Dev. (1998) [Pubmed]
  22. Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. Mansukhani, A., Ambrosetti, D., Holmes, G., Cornivelli, L., Basilico, C. J. Cell Biol. (2005) [Pubmed]
  23. Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Que, J., Okubo, T., Goldenring, J.R., Nam, K.T., Kurotani, R., Morrisey, E.E., Taranova, O., Pevny, L.H., Hogan, B.L. Development (2007) [Pubmed]
  24. Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Wood, H.B., Episkopou, V. Mech. Dev. (1999) [Pubmed]
  25. GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells. Kinoshita, K., Ura, H., Akagi, T., Usuda, M., Koide, H., Yokota, T. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  26. Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors. Gontan, C., Güttler, T., Engelen, E., Demmers, J., Fornerod, M., Grosveld, F.G., Tibboel, D., Görlich, D., Poot, R.A., Rottier, R.J. J. Cell. Biol. (2009) [Pubmed]
  27. Transplanted embryonic stem cells successfully survive, proliferate, and migrate to damaged regions of the mouse brain. Srivastava, A.S., Shenouda, S., Mishra, R., Carrier, E. Stem Cells (2006) [Pubmed]
  28. Genetic and functional differences between multipotent neural and pluripotent embryonic stem cells. D'Amour, K.A., Gage, F.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. The HMG Box Transcription Factor Sox4 Contributes to the Development of the Endocrine Pancreas. Wilson, M.E., Yang, K.Y., Kalousova, A., Lau, J., Kosaka, Y., Lynn, F.C., Wang, J., Mrejen, C., Episkopou, V., Clevers, H.C., German, M.S. Diabetes (2005) [Pubmed]
  30. Prospective identification and purification of hair cell and supporting cell progenitors from the embryonic cochlea. Doetzlhofer, A., White, P., Lee, Y.S., Groves, A., Segil, N. Brain Res. (2006) [Pubmed]
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