title: Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells.
abstract: Germ cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ cell-like cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome.
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: kurimoto@anat2.med.kyoto-u.ac.jp.
authors: Kazuki
authors: K
authors: Kurimoto
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Yukihiro
authors: Y
authors: Yabuta
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Department of Developmental Stem Cell Biology, Faculty of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan; JST, PRESTO, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Katsuhiko
authors: K
authors: Hayashi
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Hiroshi
authors: H
authors: Ohta
authors: Laboratories of Animal Resource Development and Genetic Engineering, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan.
authors: Hiroshi
authors: H
authors: Kiyonari
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Tadahiro
authors: T
authors: Mitani
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Department of Nephro-Urology, Graduate School of Medical Sciences, Nagoya City University, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors: Yoshinobu
authors: Y
authors: Moritoki
authors: Department of Nephro-Urology, Graduate School of Medical Sciences, Nagoya City University, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors: Kenjiro
authors: K
authors: Kohri
authors: Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors: Hiroshi
authors: H
authors: Kimura
authors: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin Yoshida, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Takuya
authors: T
authors: Yamamoto
authors: Laboratory of Genome Structure and Function, Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Yuki
authors: Y
authors: Katou
authors: Laboratory of Genome Structure and Function, Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin Yoshida, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: saitou@anat2.med.kyoto-u.ac.jp.
authors: Mitinori
authors: M
authors: Saitou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D000066473:Embryonic Germ Cells / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology*; D044127:Epigenesis, Genetic; D063185:Epigenetic Repression; D057890:Epigenomics; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D051379:Mice; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D006657:Histones; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C489675:Klf9 protein, mouse; C513258:Prdm1 protein, mouse; C088144:HoxA protein