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Two waves of de novo methylation during mouse germ cell development

Molaro, Antoine and Falciatori, Ilaria and Hodges, Emily and Aravin, Alexei A. and Marran, Krista and Rafii, Shahin and McCombie, W. Richard and Smith, Andrew D. and Hannon, Gregory J. (2014) Two waves of de novo methylation during mouse germ cell development. Genes and Development, 28 (14). pp. 1544-1549. ISSN 0890-9369. PMCID PMC4102761.

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During development, mammalian germ cells reprogram their epigenomes via a genome-wide erasure and de novo rewriting of DNA methylation marks. We know little of how methylation patterns are specifically determined. The piRNA pathway is thought to target the bulk of retrotransposon methylation. Here we show that most retrotransposon sequences are modified by default de novo methylation. However, potentially active retrotransposon copies evade this initial wave, likely mimicking features of protein-coding genes. These elements remain transcriptionally active and become targets of piRNA-mediated methylation. Thus, we posit that these two waves play essential roles in resetting germ cell epigenomes at each generation.

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Additional Information:© 2014 Molaro et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at Received April 25, 2014; revised version accepted June 16, 2014. We acknowledge members of the Hannon and Smith laboratories for advice on experimental design, and especially Assaf Gordon, the Cold Spring Harbor Laboratory Bioinformatics Shared Resource, Emily Lee, and Maria Mosquera for technical help. We acknowledge the Cold Spring Harbor Laboratory animal facility for help with mouse handling. This research was supported through a National Institutes of Health (NIH) stimulus grant (no. 5RC2HD064459-01) and R37GM062534 to G.J.H., and NIH R01 grant HG006015 to A.D.S. Raw sequencing data were deposited for download on Sequence Read Archive under accession numbers SRP037785, SRP037807, and SRP037987.
Funding AgencyGrant Number
NIHR01 HG006015
Subject Keywords:DNA methylation; piRNA; retrotransposon; germ cells; LINE; LTR
Issue or Number:14
PubMed Central ID:PMC4102761
Record Number:CaltechAUTHORS:20140814-154014567
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Official Citation:Molaro, A., Falciatori, I., Hodges, E., Aravin, A. A., Marran, K., Rafii, S., . . . Hannon, G. J. (2014). Two waves of de novo methylation during mouse germ cell development. Genes & Development, 28(14), 1544-1549. doi: 10.1101/gad.244350.114
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:48580
Deposited By: Jason Perez
Deposited On:22 Aug 2014 06:33
Last Modified:03 Oct 2019 07:05

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