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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2819-2828
Number of pages10
JournalCell Reports
Volume16
Issue number11
DOIs
Publication statusPublished - 2016 Sep 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