Quantitative dynamics of chromatin remodeling during germ cell specification from mouse embryonic stem cells

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

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)517-532
Number of pages16
JournalCell stem cell
Volume16
Issue number5
DOIs
Publication statusPublished - May 7 2015

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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