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ID 114323
タイトル別表記
Tuning of Sry expression by H3K9 methylation and demethylation
著者
Baba, Shoko Kyoto University
Maeda, Ryo Tokushima University
宮脇, 慎吾 Tokushima University
Yamaguchi, Miyoko Tokushima University
Kitano, Satsuki Kyoto University
Miyachi, Hitoshi Kyoto University
Itoh, Akihiro RIKEN Center for Sustainable Resource Science
Yoshida, Minoru RIKEN Center for Sustainable Resource Science
資料タイプ
学術雑誌論文
抄録
Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance.
掲載誌名
PLOS Genetics
ISSN
15537390
15537404
出版者
PLOS
13
9
開始ページ
e1007034
発行日
2017-09-26
権利情報
© 2017 Kuroki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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出版社版DOI
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フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
技術支援部