High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice
- Hisato Kobayashi1,
- Takayuki Sakurai1,
- Fumihito Miura2,
- Misaki Imai3,
- Kentaro Mochiduki4,
- Eikichi Yanagisawa1,
- Akihiko Sakashita1,
- Takuya Wakai1,
- Yutaka Suzuki5,
- Takashi Ito2,
- Yasuhisa Matsui4 and
- Tomohiro Kono1,3,6
- 1Department of BioScience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan;
- 2Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo-Ku, Tokyo 113-0032, Japan;
- 3Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan;
- 4Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan;
- 5Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 227-8561, Japan
Abstract
Dynamic epigenetic reprogramming occurs during mammalian germ cell development, although the targets of this process, including DNA demethylation and de novo methylation, remain poorly understood. We performed genome-wide DNA methylation analysis in male and female mouse primordial germ cells at embryonic days 10.5, 13.5, and 16.5 by whole-genome shotgun bisulfite sequencing. Our high-resolution DNA methylome maps demonstrated gender-specific differences in CpG methylation at genome-wide and gene-specific levels during fetal germline progression. There was extensive intra- and intergenic hypomethylation with erasure of methylation marks at imprinted, X-linked, or germline-specific genes during gonadal sex determination and partial methylation at particular retrotransposons. Following global demethylation and sex determination, CpG sites switched to de novo methylation in males, but the X-linked genes appeared resistant to the wave of de novo methylation. Significant differential methylation at a subset of imprinted loci was identified in both genders, and non-CpG methylation occurred only in male gonocytes. Our data establish the basis for future studies on the role of epigenetic modifications in germline development and other biological processes.
Footnotes
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↵6 Corresponding author
E-mail tomohiro{at}nodai.ac.jp
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.148023.112.
Freely available online through the Genome Research Open Access option.
- Received August 17, 2012.
- Accepted February 8, 2013.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.