論文

査読有り 国際誌
2019年9月17日

TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression.

Scientific reports
  • Naoki Okashita
  • ,
  • Shunsuke Kuroki
  • ,
  • Ryo Maeda
  • ,
  • Makoto Tachibana

9
1
開始ページ
13462
終了ページ
13462
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-019-50058-7

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.

リンク情報
DOI
https://doi.org/10.1038/s41598-019-50058-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31530896
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748950
ID情報
  • DOI : 10.1038/s41598-019-50058-7
  • PubMed ID : 31530896
  • PubMed Central 記事ID : PMC6748950

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