A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice

By Alexei Aravin, Ravi Sachidanandam, D. Bourc’his, C. Schaefer, Dubravka Pezic, Katalin Fejes Tóth, T. Bestor, Gregory J. Hannon. Molecules and Cells, 2008

1,190 citations recorded by the source corpus.

piRNAs and Piwi proteins have been implicated in transposon control and are linked to transposon methylation in mammals. Here, we examined the construction of the piRNA system in the restricted developmental window in which methylation patterns are set during mammalian embryogenesis. We find robust expression of two Piwi family proteins, MIWI2 and MILI. Their associated piRNA profiles reveal differences from Drosophila wherein large piRNA clusters act as master regulators of silencing. Instead, in mammals, dispersed transposon copies initiate the pathway, producing primary piRNAs, which predominantly join MILI in the cytoplasm. MIWI2, whose nuclear localization and association with piRNAs depend upon MILI, is enriched for secondary piRNAs antisense to the elements that it controls. The Piwi pathway lies upstream of known mediators of DNA methylation, since piRNAs are still produced in Dnmt3L mutants, which fail to methylate transposons. This implicates piRNAs as specificity determinants of DNA methylation in germ cells.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/7cdc6507387ea20e362184e7f36deb6028960fc5

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Citations in the corpus

PIWI-interacting small RNAs: the vanguard of genome defence (2011, background): “melanogaster , piwi mutations do not affect the female germ line in mice, despite the fact that at least one member, Mili , is expressed in female germ cells together with transposon-derived piRNA”
Small RNA sorting: matchmaking for Argonautes (2010, background): “Some piRNAs in flies and mammals must associate with particular Piwi-family proteins — that is, PIWI and MIWI2, respectively — which enable these small RNAs to enter the nucleus, where they are thought to induce transcriptional repression through changes in chromatin structure or DNA methylation, re”
Establishing, maintaining and modifying DNA methylation patterns in plants and animals (2010, background): “However, subsequent analyses of piRNA populations isolated at earlier stages of mouse development revealed an enrichment in repetitive DNA sequence”
Small silencing RNAs: an expanding universe (2009, neutral): “Both MILI and MIWI2 are expressed during this period, and Miwi2 - and Mili -deficient mice lose DNA methylation marks on transposon”
Transcriptional Silencing of Transposons by Piwi and Maelstrom and Its Impact on Chromatin State and Gene Expression (2012, neutral): “Mael is evolutionarily conserved, and its mouse homolog is required for TE silencing in testes (Aravin et al., 2009).”
Pollutants inducing epigenetic changes and diseases (2019, background): “Methylation of DNA is crucial for the proper development and plays a major role in most of the process such as repression of transposable elements (Aravin et al. 2008; Bird 1992), lyonization (Richardson and Yung 1999; Rideout et al.”