Multiple Epigenetic Mechanisms and the piRNA Pathway Enforce LINE1 Silencing during Adult Spermatogenesis

Monica Di Giacomo, Stefano Comazzetto, Harpreet Saini, Serena De Fazio, Claudia Carrieri, Marcos Morgan, Lina Vasiliauskaite, Vladimir Benes, Anton J. Enright, Donal O'Carroll*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Transposons present an acute challenge to the germline, and mechanisms that repress their activity are essential for transgenerational genomic integrity. LINE1 (L1) is the most successful retrotransposon and is epigenetically repressed by CpG DNA methylation. Here, we identify two additional important mechanisms by which L1 is repressed during spermatogenesis. We demonstrate that the Piwi protein Mili and the piRNA pathway are required to posttranscriptionally silence L1 in meiotic pachytene cells even in the presence of normal L1 DNA methylation. Strikingly, in the absence of both a functional piRNA pathway and DNA methylation, L1 elements are normally repressed in mitotic stages of spermatogenesis. Accordingly, we find that the euchromatic repressive histone H3 dimethylated lysine 9 modification cosuppresses L1 expression therein. We demonstrate the existence of multiple epigenetic mechanisms that in conjunction with the piRNA pathway sequentially enforce L1 silencing and genomic stability during mitotic and meiotic stages of adult spermatogenesis.

Original languageEnglish
Pages (from-to)601-608
Number of pages8
JournalMolecular Cell
Volume50
Issue number4
DOIs
Publication statusPublished - 23 May 2013

Keywords

  • MALE GERM-CELLS
  • HISTONE METHYLTRANSFERASE
  • DNA METHYLATION
  • MOUSE TESTIS
  • MICE
  • PIWI
  • MILI
  • AMPLIFICATION
  • EXPRESSION
  • MEIOSIS

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