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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2756-2765
Number of pages10
JournalCell Reports
Volume20
Issue number12
DOIs
Publication statusPublished - 2017 Sep 19

Fingerprint

Zygote
Protein-Arginine N-Methyltransferases
Histones
Arginine
Gonads
Genes
Mothers
Genome
Protamines
DNA
Enzymes
Chromatin
Assays
Fertilization
Oocytes

Keywords

  • active DNA demethylation
  • fertilization
  • histone arginine methylation
  • histone variant
  • zygotes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hatanaka, Y., Tsusaka, T., Shimizu, N., Morita, K., Suzuki, T., Machida, S., ... 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

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

In: Cell Reports, Vol. 20, No. 12, 19.09.2017, p. 2756-2765.

Research output: Contribution to journalArticle

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, vol. 20, no. 12, pp. 2756-2765. https://doi.org/10.1016/j.celrep.2017.08.088
Hatanaka Y, Tsusaka T, Shimizu N, Morita K, Suzuki T, Machida S et al. Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes. Cell Reports. 2017 Sep 19;20(12):2756-2765. https://doi.org/10.1016/j.celrep.2017.08.088
Hatanaka, Yuki ; Tsusaka, Takeshi ; Shimizu, Natsumi ; Morita, Kohtaro ; Suzuki, Takehiro ; Machida, Shinichi ; Satoh, Manabu ; Honda, Arata ; Hirose, Michiko ; Kamimura, Satoshi ; Ogonuki, Narumi ; Nakamura, Toshinobu ; Inoue, Kimiko ; Hosoi, Yoshihiko ; Dohmae, Naoshi ; Nakano, Toru ; Kurumizaka, Hitoshi ; Matsumoto, Kazuya ; Shinkai, Yoichi ; Ogura, Atsuo. / Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes. In: Cell Reports. 2017 ; Vol. 20, No. 12. pp. 2756-2765.
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