High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice

Hisato Kobayashi, Takayuki Sakurai, Fumihito Miura, Misaki Imai, Kentaro Mochiduki, Eikichi Yanagisawa, Akihiko Sakashita, Takuya Wakai, Yutaka Suzuki, Takashi Ito, Yasuhisa Matsui, Tomohiro Kono

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164 Citations (Scopus)

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 genomewide 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 germlinespecific 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.

Original languageEnglish
Pages (from-to)616-627
Number of pages12
JournalGenome Research
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 2013

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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    Kobayashi, H., Sakurai, T., Miura, F., Imai, M., Mochiduki, K., Yanagisawa, E., Sakashita, A., Wakai, T., Suzuki, Y., Ito, T., Matsui, Y., & Kono, T. (2013). High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice. Genome Research, 23(4), 616-627. https://doi.org/10.1101/gr.148023.112