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

ABSTRACT: The Piwi protein Mili and the Piwi-interacting RNA (piRNA) pathway are required to establish L1 DNA methylation during epigenetic reprogramming that accompanies male germ cell development. Although Mili is expressed throughout most of adult spermatogenesis, its function therein remains unknown. We find that Mili displays a hitherto unappreciated dynamic expression profile during spermatogenesis, expressed in the mitotic spermatogonia but absent at the early meiotic stages only to reappear in late zygotene spermatocytes. Here we show using conditional mutagenesis that Mili's endonuclease activity post-transcriptionally cleaves L1 transcripts commencing upon its reappearance in late zygotene spermatocytes even in the presence of normal L1 DNA methylation

INSTRUMENT(S): Illumina Genome Analyzer IIx

ORGANISM(S): Mus musculus

SUBMITTER: Harpreet Saini

PROVIDER: E-MTAB-1557 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Di Giacomo Monica M Comazzetto Stefano S Saini Harpreet H De Fazio Serena S Carrieri Claudia C Morgan Marcos M Vasiliauskaite Lina L Benes Vladimir V Enright Anton J AJ O'Carroll Dónal D

Molecular cell 20130501 4

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 cel ...[more]

PMID: 23706823

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