DNA Methylation of Retrotransposon Genes is Regulated by Piwi Family Members MILI and MIWI2 in Murine Fetal Testes

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2008 Apr 3

PMID 18381894

Citations 441

Authors

Satomi Kuramochi-Miyagawa

Toshiaki Watanabe

Kengo Gotoh

Yasushi Totoki

Atsushi Toyoda

Masahito Ikawa

Noriko Asada

Kanako Kojima

Yuka Yamaguchi

Takashi W Ijiri

Kenichiro Hata

En Li

Yoichi Matsuda

Tohru Kimura

Masaru Okabe

Yoshiyuki Sakaki

Hiroyuki Sasaki

Toru Nakano

Affiliations

Soon will be listed here.

Abstract

Silencing of transposable elements occurs during fetal gametogenesis in males via de novo DNA methylation of their regulatory regions. The loss of MILI (miwi-like) and MIWI2 (mouse piwi 2), two mouse homologs of Drosophila Piwi, activates retrotransposon gene expression by impairing DNA methylation in the regulatory regions of the retrotransposons. However, as it is unclear whether the defective DNA methylation in the mutants is due to the impairment of de novo DNA methylation, we analyze DNA methylation and Piwi-interacting small RNA (piRNA) expression in wild-type, MILI-null, and MIWI2-null male fetal germ cells. We reveal that defective DNA methylation of the regulatory regions of the Line-1 (long interspersed nuclear elements) and IAP (intracisternal A particle) retrotransposons in the MILI-null and MIWI2-null male germ cells takes place at the level of de novo methylation. Comprehensive analysis shows that the piRNAs of fetal germ cells are distinct from those previously identified in neonatal and adult germ cells. The expression of piRNAs is reduced under MILI- and MIWI2-null conditions in fetal germ cells, although the extent of the reduction differs significantly between the two mutants. Our data strongly suggest that MILI and MIWI2 play essential roles in establishing de novo DNA methylation of retrotransposons in fetal male germ cells.

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