DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes.

By Satomi Kuramochi‐Miyagawa, Toshiaki Watanabe, Kengo Gotoh, Y. Totoki, A. Toyoda, M. Ikawa, Noriko Asada, K. Kojima, Y. Yamaguchi, Takashi W. Ijiri and 8 more. Genes & Development, 2008

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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.

Subfields: Molecular Biology, Pediatrics, Perinatology and Child Health, Plant Science

View Paper: https://www.semanticscholar.org/paper/7d92d8ac9581032452b8206efe84163dd2fb986e

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Citations in the corpus

Epigenetic reprogramming and induced pluripotency (2009, neutral): “5A) (Bostick et al., 2007; Bourc’his and Bestor, 2006; Kuramochi-Miyagawa et al., 2008; Lehnertz et al., 2003; Sharif et al., 2007; Zhu et al., 2006).”
Retrotransposons revisited: the restraint and rehabilitation of parasites. (2008, positive): “Loss of Mili and Miwi2 impairs de novo IAP and L1 promoter methylation, together with a reduction in repeat-associated piRNAs and derepression of retrotransposon transcription in male germ cells of newborn mice (Kuramochi-Miyagawa et al., 2008; reviewed in O’Donnell and Boeke, 2007, Aravin et al., 2”
Establishing, maintaining and modifying DNA methylation patterns in plants and animals (2010, background): “However, subsequent analyses of piRNA populations isolated at earlier stages of mouse development revealed an enrichment in repetitive DNA sequence”
The rise of regulatory RNA (2014, background): “Piwi and Piwi-like proteins associate with a distinctive class of small RNAs (26–30 nt; piRNAs), which act to epigenetically and post-transcriptionally silence transposons in germ cells 101–110 .”
PIWI-interacting small RNAs: the vanguard of genome defence (2011, background): “Deficiency in two members of the mouse PIWI protein family, MILI (also known as PIWI-like protein 2) and MIWI2 (also known as PIWI-like protein 4), but not the third member, MIWI (also known as PIWI-like protein 1), leads to the activation of long interspersed nuclear element (LINE) and long termina”