Academic Journal
TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression
| العنوان: | TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression |
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| المؤلفون: | Okashita, Naoki, Kuroki, Shunsuke, Maeda, Ryo, Tachibana, Makoto |
| المساهمون: | MEXT | Japan Society for the Promotion of Science |
| المصدر: | Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2019 |
| الوصف: | SRY is the master regulator of male sex determination in eutherian mammals. In mice, Sry expression is transcriptionally and epigenetically controlled in a developmental stage-specific manner. The Sry promoter undergoes demethylation in embryonic gonadal somatic cells at the sex-determining period. However, its molecular mechanism and in vivo significance remain unclear. Here, we report that the Sry promoter is actively demethylated during gonadal development, and TET2 plays a fundamental role in Sry demethylation. Tet 2-deficient mice showed absence of 5-hydroxymethylcytosine in the Sry promoter. Furthermore, Tet2 deficiency diminished Sry expression, indicating that TET2-mediated DNA demethylation regulates Sry expression positively. We previously showed that the deficiency of the H3K9 demethylase Jmjd1a compromises Sry expression and induces male-to-female sex reversal. Tet2 deficiency enhanced the sex reversal phenotype of Jmjd1a -deficient mice. Thus, TET2-mediated active DNA demethylation and JMJD1A-mediated H3K9 demethylation contribute synergistically to sex determination. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-019-50058-7 |
| الاتاحة: | http://dx.doi.org/10.1038/s41598-019-50058-7 https://www.nature.com/articles/s41598-019-50058-7.pdf https://www.nature.com/articles/s41598-019-50058-7 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.CD1BF2E9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-019-50058-7 |
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