Disease relevance of SOX2

• Mutations in SOX2 cause anophthalmia [1].
• The potential of OCT4 and SOX2 to bind to this element was verified by electrophoretic mobility shift assays with extracts from F9 embryonal carcinoma cells and embryonic germ cells derived from embryonic day 12.5 embryos [2].
• SOX2 was strongly and moderately expressed in the nuclei of the foveolar epithelium and intestinal metaplasia, respectively, the expression being much higher than that in carcinomas (p<0.0001) [3].
• SOX2 mRNA was expressed in ES cells, fetal brain, anaplastic oligodendroglioma, rhabdomyosarcoma, and small cell lung carcinoma [4].
• We wished to determine the underlying cerebral phenotype in SOX2 mutation and to test the candidacy of SOX2 as a gene contributing to human epilepsies [5].
• We identified beta-catenin as the transcription partner for SOX2 and demonstrated that SOX2 and beta-catenin act in synergy in the transcription regulation of CCND1 in breast cancer cells [6].

High impact information on SOX2

• We found that PRC2 target genes are preferentially activated during ES cell differentiation and that the ES cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these genes [7].
• Critical transcription factors, notably OCT4, SOX2, and NANOG, are necessary to maintain self-renewal and pluripotency, two properties characteristic of embryonic stem (ES) cells [8].
• Furthermore, we provide genetic and molecular evidence that SOX2 activity, in a concentration-dependent manner, plays a key role in the regulation of the NOTCH1 signaling pathway in retinal progenitor cells [9].
• Collectively, these results show that precise regulation of SOX2 dosage is critical for temporal and spatial regulation of retinal progenitor cell differentiation and provide a cellular and molecular model for understanding how hypomorphic levels of SOX2 cause retinal defects in humans [9].
• Here, we directly assessed the requirement for SOX2 during eye development by generating a gene-dosage allelic series of Sox2 mutations in the mouse [9].

Chemical compound and disease context of SOX2

• Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2+ tumours, P<0.001) [10].

Biological context of SOX2

• SOX2, a SRY-related HMG box protein, is thought to be an important transcription factor during organogenesis, including the stomach although the expression and function are unclear [3].
• These data suggest that the effects of retinoic acid on neural differentiation of NTERA2 EC cells might be mediated by modulation of SOX2 and SOX3 gene expression [11].
• Due to the pivotal role of SOX2 in the early embryogenesis, SOX2 promoter and SOX2 protein were well conserved during vertebrate evolution [4].
• Comparative genomics on SOX2 orthologs [4].
• In this study it is shown for the first time that the retinoic acid-induced neuronal differentiation of NTERA2 cells is accompanied by down-regulation of SOX2 and up-regulation of SOX3 gene during early phases of induction [11].

Anatomical context of SOX2

• Moreover, over-expression of SOX2 induced the mRNA expression of endogenous MUC5AC, a specific mucin marker for the gastric type, in COS-7 cells [3].
• Modulation of SOX2 and SOX3 gene expression during differentiation of human neuronal precursor cell line NTERA2 [11].
• Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG [12].
• The SOX2 expression pattern in developing gonads is consistent with the hypothesis that this gene plays a role in the germ cell line [13].
• We cloned and characterized the ovine SOX2 transcript using the screening of a testis (12dpp) cDNA library with a probe containing the SRY-HMG-box and we performed 3'RACE experiments [13].

Associations of SOX2 with chemical compounds

• Finally, these data demonstrated that NPCs exposed to cocaine underwent differentiation into cells expressing neuronal markers that was associated with an inhibition of SOX2 (SRY-related HMG-box gene 2), a transcription factor that inhibits NPC differentiation [14].
• Out of 31 PanIN-3s, 7 were positive (22.6%), and SOX2 protein was localized in the nuclei of cells of the basal epithelium or in the vicinity of luminal necrosis [15].
• Of interest, addition of the tyrosine phosphatase inhibitor, sodium vanadate, selectively repressed Nanog transcription without any detectable changes in upstream transcriptional regulators Oct3/4 and Sox2 [16].
• Further, SUMO-1-conjugated Sox2 at the lysine 247 or at the carboxyl terminus reduced the binding to the Fgf4 enhancer [17].
• Substitution of the target lysine to arginine lost the sumoylation but little affected transcriptional potential or nuclear localization of Sox2 [17].

Physical interactions of SOX2

• In this study, we identify a second essential HMG motif within the FGF-4 enhancer that binds the transcription factor Sox-2 [18].

Regulatory relationships of SOX2

• The SOX2 gene at 3q27 might be considered an excellent candidate gene for LMS because the corresponding protein stimulates expression of FGF4, an important signaling molecule during limb outgrowth and development [19].

Other interactions of SOX2

• In sera from 23 normal adults, no antibody was detected against SOX group B or ZIC2 proteins except for one individual with low-titer anti-SOX2 antibody [20].
• However, mutation screening failed to identify CDLS patient-specific mutations in CHRD, GSC or SOX2 [21].
• The two SOX B genes SOX2 and SOX14 co-localize to chromosome 3q in humans [22].
• We identified an ES cell-specific enhancer upstream of the Lefty1 promoter that contains binding sites for Oct3/4 and Sox2 [23].
• Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2 [24].

Analytical, diagnostic and therapeutic context of SOX2

• METHODS: We examined high-resolution MRI scans in four patients with SOX2 mutations, two of whom had seizures [5].
• Our immunohistochemistry data suggest that MUC5AC and SOX2 are associated with the pancreatobiliary phenotype of ampulla of vater carcinoma and involved in later events in carcinogenesis, such as invasion and metastasis [25].
• Prenatal diagnosis of primary anophthalmia with a 3q27 interstitial deletion involving SOX2 [26].
• Identification of Sox2 as a novel c-myc BUR-binding protein was achieved through yeast one-hybrid screening and the Sox2/DNA interaction was confirmed by electrophoretic mobility shift assay and immunoprecipitation with Sox2 antibody [27].

References