title: Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis.
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.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, Via Ramarini 32, 00015 Monterotondo Scalo, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Di Giacomo
authors.forename: Stefano
authors.initials: S
authors.lastname: Comazzetto
authors.forename: Harpreet
authors.initials: H
authors.lastname: Saini
authors.forename: Serena
authors.initials: S
authors.lastname: De Fazio
authors.forename: Claudia
authors.initials: C
authors.lastname: Carrieri
authors.forename: Marcos
authors.initials: M
authors.lastname: Morgan
authors.forename: Lina
authors.initials: L
authors.lastname: Vasiliauskaite
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.forename: Dónal
authors.initials: D
authors.lastname: O'Carroll
mesh_terms: D000367:Age Factors; D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008938:Mitosis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D006657:Histones; C448521:Piwil2 protein, mouse; D034741:RNA, Small Interfering; D008239:Lysine