High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice
- Hisato Kobayashi1,
- Takayuki Sakurai1,
- Fumihito Miura2,
- Misaki Imai1,
- Kentaro Mochiduki3,
- Eikichi Yanagisawa1,
- Akihiko Sakashita1,
- Takuya Wakai1,
- Yutaka Suzuki2,
- Takashi Ito2,
- Yasuhisa Matsui3 and
- Tomohiro Kono1,4
- ↵* Corresponding author; email: tomohiro{at}nodai.ac.jp
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 day 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.
- Received August 17, 2012.
- Accepted February 8, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
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