title: Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice.
abstract: 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.
authors.affiliation: Laboratory for Mammalian Germ Cell Biology, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Seki
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamaji
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yabuta
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sano
authors.forename: Mayo
authors.initials: M
authors.lastname: Shigeta
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Matsui
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
authors.forename: Makoto
authors.initials: M
authors.lastname: Tachibana
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Mitinori
authors.initials: M
authors.lastname: Saitou
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D016195:G2 Phase; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases; D012319:RNA Polymerase II / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C462180:Dppa3 protein, mouse; D006657:Histones; C477342:Nanos3 protein, mouse; C513258:Prdm1 protein, mouse; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D010089:Oxidoreductases, N-Demethylating; D000076983:Histone Methyltransferases; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases; C513479:GLP protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II