MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells

Kanako Kojima-Kita, Satomi Kuramochi-Miyagawa, Ippei Nagamori, Narumi Ogonuki, Atsuo Ogura, Hidetoshi Hasuwa, Takashi Akazawa, Norimitsu Inoue, Toru Nakano

研究成果: Article

16 引用 (Scopus)

抜粋

During the development of mammalian embryonic germ cells, global demethylation and de novo DNA methylation take place. In mouse embryonic germ cells, two PIWI family proteins, MILI and MIWI2, are essential for the de novo DNA methylation of retrotransposons, presumably through PIWI-interacting RNAs (piRNAs). Although piRNA-associated MIWI2 has been reported to play critical roles in the process, its molecular mechanisms have remained unclear. To identify the mechanism, transgenic mice were produced; they contained a fusion protein of MIWI2 and a zinc finger (ZF) that recognized the promoter region of a type A LINE-1 gene. The ZF-MIWI2 fusion protein brought about DNA methylation, suppression of the type A LINE-1 gene, and a partial rescue of the impaired spermatogenesis of MILI-null mice. In addition, ZF-MIWI2 was associated with the proteins involved in DNA methylation. These data indicate that MIWI2 functions as an effector of de novo DNA methylation of the retrotransposon.

元の言語English
ページ(範囲)2819-2828
ページ数10
ジャーナルCell Reports
16
発行部数11
DOI
出版物ステータスPublished - 2016 9 13

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kojima-Kita, K., Kuramochi-Miyagawa, S., Nagamori, I., Ogonuki, N., Ogura, A., Hasuwa, H., Akazawa, T., Inoue, N., & Nakano, T. (2016). MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells. Cell Reports, 16(11), 2819-2828. https://doi.org/10.1016/j.celrep.2016.08.027