| First Author | Okashita N | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 13462 |
| PubMed ID | 31530896 | Mgi Jnum | J:284860 |
| Mgi Id | MGI:6389449 | Doi | 10.1038/s41598-019-50058-7 |
| Citation | Okashita N, et al. (2019) TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression. Sci Rep 9(1):13462 |
| abstractText | 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. Tet2-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. |
