Journal
MOLECULAR CELL
Volume 50, Issue 4, Pages 601-608Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2013.04.026
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Funding
- European Research Council under the European Union's Seventh Framework Programme (FP7)/ERC [ERC-310206]
- BBSRC [BB/J01589X/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J01589X/1] Funding Source: researchfish
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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.
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