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Publication : Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis.

First Author  Di Giacomo M Year  2013
Journal  Mol Cell Volume  50
Issue  4 Pages  601-8
PubMed ID  23706823 Mgi Jnum  J:199259
Mgi Id  MGI:5501381 Doi  10.1016/j.molcel.2013.04.026
Citation  Di Giacomo M, et al. (2013) Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis. Mol Cell 50(4):601-8
abstractText  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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