| 11553215 | TOX3 regulates neural progenitor identity. | Sahu SK, etal., Biochim Biophys Acta. 2016 Jul;1859(7):833-40. doi: 10.1016/j.bbagrm.2016.04.005. Epub 2016 Apr 11. | The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains larg ely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromatin immunoprecipitation assays. In line with this, over-expression of Tox3 increased Nestin promoter activity, which was cooperatively enhanced by treatment with the stem cell self-renewal promoting Notch ligand Jagged and repressed by pharmacological inhibition of Notch signaling. Knockdown of Tox3 in the subventricular zone of E12.5 mouse embryos by in utero electroporation of Tox3 shRNA revealed a reduced Nestin expression and decreased proliferation at E14 and a reduced migration to the cortical plate in E16 embryos in electroporated cells. Together, these results argue for a role of Tox3 in the development of the nervous system. | 27080130 | 2016-10-01 |
| 8554462 | TOX3 regulates calcium-dependent transcription in neurons. | Yuan SH, etal., Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2909-14. doi: 10.1073/pnas.0805555106. Epub 2009 Feb 5. | We report the cloning and characterization of TOX3, a high mobility group box protein involved in mediating calcium-dependent transcription. TOX3 was identified as a calcium-dependent transactivator using the Transactivator Trap screen. We find that TOX3 interacts with both cAMP response element (CRE)-binding protein (CREB) and CREB-binding protein (CBP), and knockdown of the endogenous TOX3 by RNAi leads to significant reduction of calcium-induced c-fos expression and complete inhibition of calcium activation of the c-fos promoter. The effects of TOX3 on calcium-dependent transcription require the CRE elements. These observations identify TOX3 as an important regulator of calcium-dependent transcription and suggest that TOX3 exerts its effect on CRE-mediated transcription via its association with the CREB-CBP complex. | 19196971 | 2009-05-01 |
| 11526396 | Association of three SNPs in TOX3 and breast cancer risk: Evidence from 97275 cases and 128686 controls. | Zhang L and Long X, Sci Rep. 2015 Aug 4;5:12773. doi: 10.1038/srep12773. | The associations of SNPs in TOX3 gene with breast cancer risk were investigated by some Genome-wide association studies and epidemiological studies, but the study results were contradictory. To derive a more precise estimate of the associations, we conducted a m eta-analysis. ORs with 95% CI were used to assess the strength of association between TOX3 polymorphisms and breast cancer risk in fixed or random effect model. A total of 37 publications with 97275 cases and 128686 controls were identified. We observed that the rs3803662 C > T, rs12443621 A > G and rs8051542 C > T were all correlated with increased risk of breast cancer. In the stratified analyses by ethnicity, significantly elevated risk was detected for all genetic models of the three SNPs in Caucasians. In Asian populations, there were significant associations of rs3803662 and rs8051542 with breast cancer risk. Whereas there was no evidence for statistical significant association between the three SNPs and breast cancer risk in Africans. Additionally, we observed different associations of rs3803662 with breast cancer risk based on different ER subtype and BRCA1/BRCA2 mutation carriers. In conclusion, the meta-analysis suggested that three SNPs in TOX3 were significantly associated with breast cancer risk in different populations. | 26239137 | 1000-08-01 |
| 617154584 | Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate. | Mohamad Shah NS, etal., Mol Genet Genomic Med. 2019 May;7(5):e635. doi: 10.1002/mgg3.635. Epub 2019 Mar 28. |
BACKGROUND: Nonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.
METHODS: Genome-wide linkage analysis was carried out on eight large extended families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of LPHN2, SATB2, PVRL3, COL21A1, and TOX3 were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.
RESULTS: Genome-wide linkage analysis had discovered several genes including TOX3 and COL21A1 in four different loci 4p15.2-p16.1, 6p11.2-p12.3, 14q13-q21, and 16q12.1. There was significant decreased, p < 0.05 of SATB2, COL21A1, and TOX3 copy number in extended families compared to the normal controls.
CONCLUSION: Novel linkage evidence and significant low copy number of COL21A1 and TOX3 in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits. | 30924295 | 2019-05-01 |
