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

Cell Stem Cell. 2015 May 7;16(5):517-32. doi: 10.1016/j.stem.2015.03.002. Epub 2015 Mar 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Chromatin Assembly and Disassembly
  • Embryonic Germ Cells / physiology*
  • Embryonic Stem Cells / physiology*
  • Epigenesis, Genetic
  • Epigenetic Repression
  • Epigenomics
  • Fetal Proteins / genetics
  • Fetal Proteins / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Methylation
  • Mice
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Binding
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Fetal Proteins
  • Histones
  • Homeodomain Proteins
  • Klf9 protein, mouse
  • Kruppel-Like Transcription Factors
  • Prdm1 protein, mouse
  • T-Box Domain Proteins
  • Transcription Factors
  • HoxA protein
  • Positive Regulatory Domain I-Binding Factor 1
  • Brachyury protein

Associated data

  • GEO/GSE60018
  • GEO/GSE60204