SOX2

LIF (Leukemia inhibitory factor) signaling, which maintains pluripotency in mouse embryonic stem cells, activates Sox2 downstream of the JAK-STAT signaling pathway and subsequent activation of Klf4 (a member of the family of Kruppel-like factors). Oct-4, Sox2 and Nanog positively regulate transcription of all pluripotency circuitry proteins in the LIF pathway.{{cite journal | vauthors = Niwa H, Ogawa K, Shimosato D, Adachi K | title = A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells | journal = Nature | volume = 460 | issue = 7251 | pages = 118–122 | date = July 2009 | pmid = 19571885 | doi = 10.1038/nature08113 | s2cid = 4382543 | bibcode = 2009Natur.460..118N }}

NPM1, a transcriptional regulator involved in cell proliferation, individually forms complexes with Sox2, Oct4 and Nanog in embryonic stem cells.{{cite journal | vauthors = Johansson H, Simonsson S | title = Core transcription factors, Oct4, Sox2 and Nanog, individually form complexes with nucleophosmin (Npm1) to control embryonic stem (ES) cell fate determination | journal = Aging | volume = 2 | issue = 11 | pages = 815–822 | date = November 2010 | pmid = 21076177 | pmc = 3006024 | doi = 10.18632/aging.100222 }} These three pluripotency factors contribute to a complex molecular network that regulates a number of genes controlling pluripotency. Sox2 binds to DNA cooperatively with Oct4 at non-palindromic sequences to activate transcription of key pluripotency factors.{{cite journal | vauthors = Chambers I, Tomlinson SR | title = The transcriptional foundation of pluripotency | journal = Development | volume = 136 | issue = 14 | pages = 2311–2322 | date = July 2009 | pmid = 19542351 | pmc = 2729344 | doi = 10.1242/dev.024398 }} Surprisingly, regulation of Oct4-Sox2 enhancers can occur without Sox2, likely due to expression of other Sox proteins. However, a group of researchers concluded that the primary role of Sox2 in embryonic stem cells is controlling Oct4 expression, and they both perpetuate their own expression when expressed concurrently.{{cite journal | vauthors = Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H | display-authors = 6 | title = Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells | journal = Nature Cell Biology | volume = 9 | issue = 6 | pages = 625–635 | date = June 2007 | pmid = 17515932 | doi = 10.1038/ncb1589 | s2cid = 24074525 }}

In an experiment involving mouse embryonic stem cells, it was discovered that Sox2 in conjunction with Oct4, c-Myc and Klf4 were sufficient for producing induced pluripotent stem cells.{{cite journal | vauthors = Takahashi K, Yamanaka S | title = Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors | journal = Cell | volume = 126 | issue = 4 | pages = 663–676 | date = August 2006 | pmid = 16904174 | doi = 10.1016/j.cell.2006.07.024 | hdl-access = free | s2cid = 1565219 | hdl = 2433/159777 }} The discovery that expression of only four transcription factors was necessary to induce pluripotency allowed future regenerative medicine research to be conducted considering minor manipulations.

Loss of pluripotency is regulated by hypermethylation of some Sox2 and Oct4 binding sites in male germ cells{{cite journal | vauthors = Imamura M, Miura K, Iwabuchi K, Ichisaka T, Nakagawa M, Lee J, Kanatsu-Shinohara M, Shinohara T, Yamanaka S | display-authors = 6 | title = Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells | journal = BMC Developmental Biology | volume = 6 | pages = 34 | date = July 2006 | pmid = 16859545 | pmc = 1564388 | doi = 10.1186/1471-213X-6-34 | doi-access = free }} and post-transcriptional suppression of Sox2 by miR134.{{cite journal | vauthors = Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I | title = MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation | journal = Nature | volume = 455 | issue = 7216 | pages = 1124–1128 | date = October 2008 | pmid = 18806776 | doi = 10.1038/nature07299 | s2cid = 4330178 | bibcode = 2008Natur.455.1124T }}

Varying levels of Sox2 affect embryonic stem cells' fate of differentiation. Sox2 inhibits differentiation into the mesendoderm germ layer and promotes differentiation into neural ectoderm germ layer.{{cite journal | vauthors = Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S | title = Pluripotency factors in embryonic stem cells regulate differentiation into germ layers | journal = Cell | volume = 145 | issue = 6 | pages = 875–889 | date = June 2011 | pmid = 21663792 | pmc = 5603300 | doi = 10.1016/j.cell.2011.05.017 }} Npm1/Sox2 complexes are sustained when differentiation is induced along the ectodermal lineage, emphasizing an important functional role for Sox2 in ectodermal differentiation. The loss of Sox2 has also been shown to affect naïve pluripotency, with Sox2-depleted mouse embryonic cells becoming able to differentiate into extraembryonic trophoblast.{{cite journal | vauthors = Tremble KC, Stirparo GG, Bates LE, Maskalenka K, Stuart HT, Jones K, Andersson-Rolf A, Radzisheuskaya A, Koo BK, Bertone P, Silva JC | display-authors = 6 | title = Sox2 modulation increases naïve pluripotency plasticity | language = English | journal = iScience | volume = 24 | issue = 3 | pages = 102153 | date = March 2021 | pmid = 33665571 | pmc = 7903329 | doi = 10.1016/j.isci.2021.102153 | bibcode = 2021iSci...24j2153T }}

Deficiency of Sox2 in mice has been shown to result in neural malformities and eventually fetal death, further underlining Sox2's vital role in embryonic development.{{cite journal | vauthors = Ferri AL, Cavallaro M, Braida D, Di Cristofano A, Canta A, Vezzani A, Ottolenghi S, Pandolfi PP, Sala M, DeBiasi S, Nicolis SK | display-authors = 6 | title = Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain | journal = Development | volume = 131 | issue = 15 | pages = 3805–3819 | date = August 2004 | pmid = 15240551 | doi = 10.1242/dev.01204 | s2cid = 26059456 | doi-access = }}

In neurogenesis, Sox2 is expressed throughout developing cells in the neural tube as well as in proliferating central nervous system progenitors. However, Sox2 is downregulated during progenitors' final cell cycle during differentiation when they become post mitotic.{{cite journal | vauthors = Graham V, Khudyakov J, Ellis P, Pevny L | title = SOX2 functions to maintain neural progenitor identity | journal = Neuron | volume = 39 | issue = 5 | pages = 749–765 | date = August 2003 | pmid = 12948443 | doi = 10.1016/S0896-6273(03)00497-5 | s2cid = 17162323 | doi-access = free }} Cells expressing Sox2 are capable of both producing cells identical to themselves and differentiated neural cell types, two necessary hallmarks of stem cells. Thus signals controlling Sox2 expression in the presumptive neuronal compartment, like Notch signaling, control what size the neuronal compartment finally reaches.{{cite journal | vauthors = Liu P, Verhaar AP, Peppelenbosch MP | title = Signaling Size: Ankyrin and SOCS Box-Containing ASB E3 Ligases in Action | journal = Trends in Biochemical Sciences | volume = 44 | issue = 1 | pages = 64–74 | date = January 2019 | pmid = 30446376 | doi = 10.1016/j.tibs.2018.10.003 | s2cid = 53569740 }} Proliferation of Sox2+ neural stem cells can generate neural precursors as well as Sox2+ neural stem cell population.{{cite journal | vauthors = Suh H, Consiglio A, Ray J, Sawai T, D'Amour KA, Gage FH | title = In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus | journal = Cell Stem Cell | volume = 1 | issue = 5 | pages = 515–528 | date = November 2007 | pmid = 18371391 | pmc = 2185820 | doi = 10.1016/j.stem.2007.09.002 }} Differences in brain size between the species thus relate to the capacity of different species to maintain SOX2 expression in the developing neural systems. The difference in brain size between humans and apes, for instance, has been linked to mutations in the gene Asb11, which is an upstream activator of SOX2 in the developing neural system.{{cite journal | vauthors = Diks SH, Bink RJ, van de Water S, Joore J, van Rooijen C, Verbeek FJ, den Hertog J, Peppelenbosch MP, Zivkovic D | display-authors = 6 | title = The novel gene asb11: a regulator of the size of the neural progenitor compartment | journal = The Journal of Cell Biology | volume = 174 | issue = 4 | pages = 581–592 | date = August 2006 | pmid = 16893969 | pmc = 2064263 | doi = 10.1083/jcb.200601081 | doi-access = free }}

Induced pluripotency is possible using adult neural stem cells, which express higher levels of Sox2 and c-Myc than embryonic stem cells. Therefore, only two exogenous factors, one of which is necessarily Oct4, are sufficient for inducing pluripotent cells from neural stem cells, lessening the complications and risks associated with introducing multiple factors to induce pluripotency.{{cite journal | vauthors = Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo MJ, Ruau D, Han DW, Zenke M, Schöler HR | display-authors = 6 | title = Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors | journal = Nature | volume = 454 | issue = 7204 | pages = 646–650 | date = July 2008 | pmid = 18594515 | doi = 10.1038/nature07061 | s2cid = 4318637 | bibcode = 2008Natur.454..646K }}

Mutations in this gene have been linked with bilateral anophthalmia, a severe structural eye deformity.{{cite web | title = Entrez Gene: SOX2 SRY (sex determining region Y)-box 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6657}}

In lung development, Sox2 controls the branching morphogenesis of the bronchial tree and differentiation of the epithelium of airways. Overexpression causes an increase in neuroendocrine, gastric/intestinal and basal cells.{{cite journal | vauthors = Gontan C, de Munck A, Vermeij M, Grosveld F, Tibboel D, Rottier R | title = Sox2 is important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation | journal = Developmental Biology | volume = 317 | issue = 1 | pages = 296–309 | date = May 2008 | pmid = 18374910 | doi = 10.1016/j.ydbio.2008.02.035 | doi-access = free }} Under normal conditions, Sox2 is critical for maintaining self-renewal and appropriate proportion of basal cells in adult tracheal epithelium. However, its overexpression gives rise to extensive epithelial hyperplasia and eventually carcinoma in both developing and adult mouse lungs.{{cite journal | vauthors = Lu Y, Futtner C, Rock JR, Xu X, Whitworth W, Hogan BL, Onaitis MW | title = Evidence that SOX2 overexpression is oncogenic in the lung | journal = PLOS ONE | volume = 5 | issue = 6 | pages = e11022 | date = June 2010 | pmid = 20548776 | pmc = 2883553 | doi = 10.1371/journal.pone.0011022 | doi-access = free | bibcode = 2010PLoSO...511022L }}

In squamous cell carcinoma, gene amplifications frequently target the 3q26.3 region. The gene for Sox2 lies within this region, which effectively characterizes Sox2 as an oncogene, although in adenocarcinoma of the esophagus loss of Sox2 is strongly associated with worse prognosis, effectively characterising Sox2 as a tumor suppressor. It thus fair to say that the function of SOX2 in cancer is pleiotropic. {{cite journal | vauthors = van Olphen SH, Biermann K, Shapiro J, Wijnhoven BP, Toxopeus EL, van der Gaast A, Stoop HA, van Lanschot JJ, Spaander MC, Bruno MJ, Looijenga LH | display-authors = 6 | title = P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy | journal = Annals of Surgery | volume = 265 | issue = 2 | pages = 347–355 | date = February 2017 | pmid = 28059963 | doi = 10.1097/SLA.0000000000001625 | s2cid = 19544093 }} Sox2 is a key upregulated factor in lung squamous cell carcinoma, directing many genes involved in tumor progression. Sox2 overexpression cooperates with loss of Lkb1 expression to promote squamous cell lung cancer in mice.{{cite journal | vauthors = Mukhopadhyay A, Berrett KC, Kc U, Clair PM, Pop SM, Carr SR, Witt BL, Oliver TG | display-authors = 6 | title = Sox2 cooperates with Lkb1 loss in a mouse model of squamous cell lung cancer | journal = Cell Reports | volume = 8 | issue = 1 | pages = 40–49 | date = July 2014 | pmid = 24953650 | pmc = 4410849 | doi = 10.1016/j.celrep.2014.05.036 }} Its overexpression also activates cellular migration and anchorage-independent growth.{{cite journal | vauthors = Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembelé D, Martinet N, Thibault C, Huelsken J, Brambilla E, du Manoir S | display-authors = 6 | title = SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas | journal = PLOS ONE | volume = 5 | issue = 1 | pages = e8960 | date = January 2010 | pmid = 20126410 | pmc = 2813300 | doi = 10.1371/journal.pone.0008960 | doi-access = free | bibcode = 2010PLoSO...5.8960H }}

Sox2 expression is also found in high gleason grade prostate cancer, and promotes castration-resistant prostate cancer growth.{{cite journal | vauthors = Kregel S, Kiriluk KJ, Rosen AM, Cai Y, Reyes EE, Otto KB, Tom W, Paner GP, Szmulewitz RZ, Vander Griend DJ | display-authors = 6 | title = Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer | journal = PLOS ONE | volume = 8 | issue = 1 | pages = e53701 | year = 2013 | pmid = 23326489 | pmc = 3543364 | doi = 10.1371/journal.pone.0053701 | doi-access = free | bibcode = 2013PLoSO...853701K }}

The ectopic expression of SOX2 may be related to abnormal differentiation of colorectal cancer cells.{{cite journal | vauthors = Tani Y, Akiyama Y, Fukamachi H, Yanagihara K, Yuasa Y | title = Transcription factor SOX2 up-regulates stomach-specific pepsinogen A gene expression | journal = Journal of Cancer Research and Clinical Oncology | volume = 133 | issue = 4 | pages = 263–269 | date = April 2007 | pmid = 17136346 | doi = 10.1007/s00432-006-0165-x | s2cid = 33410257 }}

Sox2 has been shown to be relevant in the development of Tamoxifen resistance in breast cancer.{{cite journal | vauthors = Piva M, Domenici G, Iriondo O, Rábano M, Simões BM, Comaills V, Barredo I, López-Ruiz JA, Zabalza I, Kypta R, Vivanco M | display-authors = 6 | title = Sox2 promotes tamoxifen resistance in breast cancer cells | journal = EMBO Molecular Medicine | volume = 6 | issue = 1 | pages = 66–79 | date = January 2014 | pmid = 24178749 | pmc = 3936493 | doi = 10.1002/emmm.201303411 }}

In Glioblastoma multiforme, Sox2 is a well-established stem cell transcription factor needed to induce and maintain stemness properties of glioblastoma cancer cells.{{cite journal | vauthors = Ikushima H, Todo T, Ino Y, Takahashi M, Miyazawa K, Miyazono K | title = Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors | journal = Cell Stem Cell | volume = 5 | issue = 5 | pages = 504–514 | date = November 2009 | pmid = 19896441 | doi = 10.1016/j.stem.2009.08.018 | doi-access = free }}{{cite journal | vauthors = Gangemi RM, Griffero F, Marubbi D, Perera M, Capra MC, Malatesta P, Ravetti GL, Zona GL, Daga A, Corte G | display-authors = 6 | title = SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity | journal = Stem Cells | volume = 27 | issue = 1 | pages = 40–48 | date = January 2009 | pmid = 18948646 | doi = 10.1634/stemcells.2008-0493 | s2cid = 19125999 | doi-access = free }}

There are three thyroid hormone response elements (TREs) in the region upstream of the Sox2 promoter. This region is known as the enhancer region. Studies have suggested that thyroid hormone (T3) controls Sox2 expression via the enhancer region. The expression of TRα1 (thyroid hormone receptor) is increased in proliferating and migrating neural stem cells. It has therefore been suggested that transcriptional repression of Sox2, mediated by the thyroid hormone signaling axis, allows for neural stem cell commitment and migration from the sub-ventricular zone. A deficiency of thyroid hormone, particularly during the first trimester, will lead to abnormal central nervous system development.{{cite journal | vauthors = López-Juárez A, Remaud S, Hassani Z, Jolivet P, Pierre Simons J, Sontag T, Yoshikawa K, Price J, Morvan-Dubois G, Demeneix BA | display-authors = 6 | title = Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche | journal = Cell Stem Cell | volume = 10 | issue = 5 | pages = 531–543 | date = May 2012 | pmid = 22560077 | doi = 10.1016/j.stem.2012.04.008 | doi-access = free }}

Further supporting this conclusion is the fact that hypothyroidism during fetal development can result in a variety of neurological deficiencies, including cretinism, characterized by stunted physical development and mental retardation.

Hypothyroidism can arise from a multitude of causes, and is commonly remedied with hormone treatments such as the commonly used Levothyroxine.{{ cite encyclopedia | author = Wisse B | title = Hypothyroidism: MedlinePlus Medical Encyclopedia. | publisher = U.S National Library of Medicine | access-date = 10 April 2014 | url = https://www.nlm.nih.gov/medlineplus/ency/article/000353.htm }}

SOX2 has been shown to interact with PAX6,{{cite journal | vauthors = Aota S, Nakajima N, Sakamoto R, Watanabe S, Ibaraki N, Okazaki K | title = Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene | journal = Developmental Biology | volume = 257 | issue = 1 | pages = 1–13 | date = May 2003 | pmid = 12710953 | doi = 10.1016/S0012-1606(03)00058-7 | doi-access = }} NPM1, and Oct4. SOX2 has been found to cooperatively regulate Rex1 with Oct3/4.{{cite journal | vauthors = Shi W, Wang H, Pan G, Geng Y, Guo Y, Pei D | title = Regulation of the pluripotency marker Rex-1 by Nanog and Sox2 | journal = The Journal of Biological Chemistry | volume = 281 | issue = 33 | pages = 23319–23325 | date = August 2006 | pmid = 16714766 | doi = 10.1074/jbc.M601811200 | doi-access = free }}

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{{refbegin|32em}}

• {{cite journal | vauthors = Kamachi Y, Uchikawa M, Kondoh H | title = Pairing SOX off: with partners in the regulation of embryonic development | journal = Trends in Genetics | volume = 16 | issue = 4 | pages = 182–187 | date = April 2000 | pmid = 10729834 | doi = 10.1016/S0168-9525(99)01955-1 }}
• {{cite journal | vauthors = Schepers GE, Teasdale RD, Koopman P | title = Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families | journal = Developmental Cell | volume = 3 | issue = 2 | pages = 167–170 | date = August 2002 | pmid = 12194848 | doi = 10.1016/S1534-5807(02)00223-X | doi-access = free }}
• {{cite journal | vauthors = Hever AM, Williamson KA, van Heyningen V | title = Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2 | journal = Clinical Genetics | volume = 69 | issue = 6 | pages = 459–470 | date = June 2006 | pmid = 16712695 | doi = 10.1111/j.1399-0004.2006.00619.x | s2cid = 5676139 }}
• {{cite journal | vauthors = Yuan H, Corbi N, Basilico C, Dailey L | title = Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3 | journal = Genes & Development | volume = 9 | issue = 21 | pages = 2635–2645 | date = November 1995 | pmid = 7590241 | doi = 10.1101/gad.9.21.2635 | doi-access = free }}
• {{cite journal | vauthors = Stevanovic M, Zuffardi O, Collignon J, Lovell-Badge R, Goodfellow P | title = The cDNA sequence and chromosomal location of the human SOX2 gene | journal = Mammalian Genome | volume = 5 | issue = 10 | pages = 640–642 | date = October 1994 | pmid = 7849401 | doi = 10.1007/BF00411460 | s2cid = 10841620 }}
• {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
• {{cite journal | vauthors = Helland R, Berglund GI, Otlewski J, Apostoluk W, Andersen OA, Willassen NP, Smalås AO | title = High-resolution structures of three new trypsin-squash-inhibitor complexes: a detailed comparison with other trypsins and their complexes | journal = Acta Crystallographica. Section D, Biological Crystallography | volume = 55 | issue = Pt 1 | pages = 139–148 | date = January 1999 | pmid = 10089404 | doi = 10.1107/S090744499801052X | bibcode = 1999AcCrD..55..139H | doi-access = }}
• {{cite journal | vauthors = Güre AO, Stockert E, Scanlan MJ, Keresztes RS, Jäger D, Altorki NK, Old LJ, Chen YT | display-authors = 6 | title = Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 8 | pages = 4198–4203 | date = April 2000 | pmid = 10760287 | pmc = 18195 | doi = 10.1073/pnas.97.8.4198 | doi-access = free | bibcode = 2000PNAS...97.4198G }}
• {{cite journal | vauthors = Ambrosetti DC, Schöler HR, Dailey L, Basilico C | title = Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer | journal = The Journal of Biological Chemistry | volume = 275 | issue = 30 | pages = 23387–23397 | date = July 2000 | pmid = 10801796 | doi = 10.1074/jbc.M000932200 | doi-access = free }}
• {{cite journal | vauthors = Kamachi Y, Uchikawa M, Tanouchi A, Sekido R, Kondoh H | title = Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development | journal = Genes & Development | volume = 15 | issue = 10 | pages = 1272–1286 | date = May 2001 | pmid = 11358870 | pmc = 313803 | doi = 10.1101/gad.887101 }}
• {{cite journal | vauthors = Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, FitzPatrick DR | display-authors = 6 | title = Mutations in SOX2 cause anophthalmia | journal = Nature Genetics | volume = 33 | issue = 4 | pages = 461–463 | date = April 2003 | pmid = 12612584 | doi = 10.1038/ng1120 | doi-access = free }}
• {{cite journal | vauthors = Wiebe MS, Nowling TK, Rizzino A | title = Identification of novel domains within Sox-2 and Sox-11 involved in autoinhibition of DNA binding and partnership specificity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 20 | pages = 17901–17911 | date = May 2003 | pmid = 12637543 | doi = 10.1074/jbc.M212211200 | doi-access = free }}
• {{cite journal | vauthors = Aota S, Nakajima N, Sakamoto R, Watanabe S, Ibaraki N, Okazaki K | title = Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene | journal = Developmental Biology | volume = 257 | issue = 1 | pages = 1–13 | date = May 2003 | pmid = 12710953 | doi = 10.1016/S0012-1606(03)00058-7 | doi-access = }}
• {{cite journal | vauthors = Schepers G, Wilson M, Wilhelm D, Koopman P | title = SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro | journal = The Journal of Biological Chemistry | volume = 278 | issue = 30 | pages = 28101–28108 | date = July 2003 | pmid = 12732652 | doi = 10.1074/jbc.M304067200 | doi-access = free }}
• {{cite journal | vauthors = Reményi A, Lins K, Nissen LJ, Reinbold R, Schöler HR, Wilmanns M | title = Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers | journal = Genes & Development | volume = 17 | issue = 16 | pages = 2048–2059 | date = August 2003 | pmid = 12923055 | pmc = 196258 | doi = 10.1101/gad.269303 }}
• {{cite journal | vauthors = Williams DC, Cai M, Clore GM | title = Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex | journal = The Journal of Biological Chemistry | volume = 279 | issue = 2 | pages = 1449–1457 | date = January 2004 | pmid = 14559893 | doi = 10.1074/jbc.M309790200 | doi-access = free }}
• {{cite journal | vauthors = Tsukamoto T, Inada K, Tanaka H, Mizoshita T, Mihara M, Ushijima T, Yamamura Y, Nakamura S, Tatematsu M | display-authors = 6 | title = Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia | journal = Journal of Cancer Research and Clinical Oncology | volume = 130 | issue = 3 | pages = 135–145 | date = March 2004 | pmid = 14655050 | doi = 10.1007/s00432-003-0519-6 | s2cid = 19831132 }}

{{refend}}

• [https://web.archive.org/web/20090628185523/http://jura.wi.mit.edu/young_public/hESregulation/index.html Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells]
• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sox2 GeneReviews/NCBI/NIH/UW entry on SOX2-related eye disorders]
• [http://www.jove.com/index/details.stp?ID=734 Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4 (Journal of Visualized Experiments)] {{Webarchive|url=https://web.archive.org/web/20080409111706/http://www.jove.com/index/details.stp?ID=734 |date=9 April 2008 }}
• [https://www.ncbi.nlm.nih.gov/books/NBK1378/ GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview]
• {{PDBe-KB2|P48431|Human Transcription factor SOX-2}}
• {{PDBe-KB2|P48432|Mouse Transcription factor SOX-2}}

{{PDB Gallery|geneid=6657}}

{{Transcription factors|g4}}

{{DEFAULTSORT:Sox2}}

Category:Transcription factors