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First published online 13 June 2007
doi: 10.1242/dev.005611


Development 134, 2627-2638 (2007)
Published by The Company of Biologists 2007


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

Yoshiyuki Seki1, Masashi Yamaji1,2, Yukihiro Yabuta1, Mitsue Sano1,3, Mayo Shigeta1, Yasuhisa Matsui4, Yumiko Saga5, Makoto Tachibana6, Yoichi Shinkai6 and Mitinori Saitou1,2,7,*

1 Laboratory for Mammalian Germ Cell Biology, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
2 Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
3 Department of Biosystems Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
4 Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
5 Department of Genetics and Division of Mammalian Development, National Institute of Genetics, SOKENDAI, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
6 Department of Cell Biology, Institute for Virus Research, Kyoto University, Shogoin Kawara-cho, Kyoto 606-8507, Japan.
7 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan.

* Author for correspondence (e-mail: saitou{at}cdb.riken.jp)

Accepted 10 May 2007

We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 dimethylation (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.

Key words: Primordial germ cells (PGCs), Histone modifications, Reprogramming, Cell cycle, Epigenetics, Mouse


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