Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice

Yoshiyuki Sekl, Masashi Yamaji, Yukihiro Yabuta, Mitsue Sano, Mayo Shigeta, Yasuhisa Matsui, Yumiko Saga, Makoto Tachibana, Yoichi Shinkai, Mitinori Saitou

Research output: Contribution to journalArticlepeer-review

304 Citations (Scopus)

Abstract

We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 di-methylation (H3K9me2), and instead acquire high levels of tri-methylation of H3K27 (H3K27me3) during their migration, a process that might be crucial for the re-establishment of potential totipotency in the germline. We here explored a cellular dynamics associated with this epigenetic reprogramming. We found that PGCs undergo erasure of H3K9me2 and upregulation of H3K27me3 in a progressive, cell-by-cell manner, presumably depending on their developmental maturation. Before or concomitant with the onset of H3K9 demethylation, PGCs entered the G2 arrest of the cell cycle, which apparently persisted until they acquired high H3K27me3 levels. Interestingly, PGCs exhibited repression of RNA polymerase II-dependent transcription, which began after the onset of H3K9me2 reduction in the G2 phase and tapered off after the acquisition of high-level H3K27me3. The epigenetic reprogramming and transcriptional quiescence were independent from the function of Nanos3. We found that before H3K9 demethylation, PGCs exclusively repress an essential histone methyltransferase, GLP, without specifically upregulating histone demethylases. We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs.

Original languageEnglish
Pages (from-to)2627-2638
Number of pages12
JournalDevelopment
Volume134
Issue number14
DOIs
Publication statusPublished - 2007 Jul

Keywords

  • Cell cycle
  • Epigenetics
  • Histone modifications
  • Mouse
  • Primordial germ cells (PGCs)
  • Reprogramming

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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