Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells. 2015

Kazuki Kurimoto, and Yukihiro Yabuta, and Katsuhiko Hayashi, and Hiroshi Ohta, and Hiroshi Kiyonari, and Tadahiro Mitani, and Yoshinobu Moritoki, and Kenjiro Kohri, and Hiroshi Kimura, and Takuya Yamamoto, and Yuki Katou, and Katsuhiko Shirahige, and Mitinori Saitou
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.

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.

UI MeSH Term Description Entries
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005326 Fetal Proteins Proteins that are preferentially expressed or upregulated during FETAL DEVELOPMENT. Fetoprotein,Fetoproteins,Proteins, Fetal
D006657 Histones Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D000066473 Embryonic Germ Cells PLURIPOTENT STEM CELLS that are derived from early GERM CELLS. EG Cells,Germ Cells, Embryonic,Cell, EG,Cell, Embryonic Germ,Cells, EG,Cells, Embryonic Germ,EG Cell,Embryonic Germ Cell,Germ Cell, Embryonic
D000074462 Positive Regulatory Domain I-Binding Factor 1 A transcriptional repressor protein that contains an N-terminal PR-SET domain, four C-terminal CYS2-HIS2 ZINC FINGERS, and binds the PRDI element in the INTERFERON-BETA gene. It has methyltransferase activity and mediates gene transcription in tissue-specific innate and adaptive immune lymphocyte T-CELLS, repressing expression of proteins that promote exit of these tissue-specific T-cell populations from non-lymphoid organs. B Lymphocyte-Induced Maturation Protein 1,BLIMP1 Protein,PRDI-BF1 Protein,PRDM1 Protein,B Lymphocyte Induced Maturation Protein 1,PRDI BF1 Protein,Positive Regulatory Domain I Binding Factor 1
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription

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