3 years ago

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

Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes
Naoshi Dohmae, Kimiko Inoue, Michiko Hirose, Toru Nakano, Yuki Hatanaka, Hitoshi Kurumizaka, Takehiro Suzuki, Narumi Ogonuki, Yoshihiko Hosoi, Arata Honda, Atsuo Ogura, Satoshi Kamimura, Natsumi Shimizu, Kohtaro Morita, Yoichi Shinkai, Kazuya Matsumoto, Toshinobu Nakamura, Manabu Satoh, Shinichi Machida, Takeshi Tsusaka

Summary

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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31230-5

DOI: 10.1016/j.celrep.2017.08.088

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