Published July 15, 2014 | Version Supplemental Material + Published
Journal Article Open

Two waves of de novo methylation during mouse germ cell development

  • 1. ROR icon Cold Spring Harbor Laboratory
  • 2. ROR icon California Institute of Technology
  • 3. ROR icon University of Southern California

Abstract

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.

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 http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. 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.

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Published - Genes_Dev.-2014-Molaro-1544-9.pdf

Supplemental Material - SuppMaterial_REV.pdf

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Additional details

Identifiers

PMCID
PMC4102761
Eprint ID
48580
Resolver ID
CaltechAUTHORS:20140814-154014567

Funding

NIH
5RC2HD064459-01
NIH
R37GM062534
NIH
R01 HG006015

Dates

Created
2014-08-22
Created from EPrint's datestamp field
Updated
2021-11-10
Created from EPrint's last_modified field