Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes

Yuki Hatanaka, Takeshi Tsusaka, Natsumi Shimizu, Kohtaro Morita, Takehiro Suzuki, Shinichi Machida, Manabu Satoh, Arata Honda, Michiko Hirose, Satoshi Kamimura, Narumi Ogonuki, Toshinobu Nakamura, Kimiko Inoue, Yoshihiko Hosoi, Naoshi Dohmae, Toru Nakano, Hitoshi Kurumizaka, Kazuya Matsumoto, Yoichi Shinkai, Atsuo Ogura

研究成果: Article

10 引用 (Scopus)

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At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a. Mettl23 interacts with Tet3, a 5mC-oxidizing enzyme responsible for active DNA demethylation, by binding to another maternal factor, GSE (gonad-specific expression). Depletion of Mettl23 from oocytes resulted in impaired accumulation of GSE, Tet3, and 5hmC in the male pronucleus, suggesting that Mettl23 may recruit GSE-Tet3 to chromatin. Our findings establish H3R17me2a and its catalyzing enzyme Mettl23 as key regulators of paternal genome reprogramming.

元の言語English
ページ(範囲)2756-2765
ページ数10
ジャーナルCell Reports
20
発行部数12
DOI
出版物ステータスPublished - 2017 9 19

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Hatanaka, Y., Tsusaka, T., Shimizu, N., Morita, K., Suzuki, T., Machida, S., Satoh, M., Honda, A., Hirose, M., Kamimura, S., Ogonuki, N., Nakamura, T., Inoue, K., Hosoi, Y., Dohmae, N., Nakano, T., Kurumizaka, H., Matsumoto, K., Shinkai, Y., & Ogura, A. (2017). Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes. Cell Reports, 20(12), 2756-2765. https://doi.org/10.1016/j.celrep.2017.08.088