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Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells.
- Source :
-
Cell stem cell [Cell Stem Cell] 2015 May 07; Vol. 16 (5), pp. 517-32. Date of Electronic Publication: 2015 Mar 19. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Differentiation
Cells, Cultured
Chromatin Assembly and Disassembly
Epigenesis, Genetic
Epigenetic Repression
Epigenomics
Fetal Proteins genetics
Histones genetics
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
Transcription Factors genetics
Embryonic Germ Cells physiology
Embryonic Stem Cells physiology
Fetal Proteins metabolism
Histones metabolism
T-Box Domain Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-9777
- Volume :
- 16
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell stem cell
- Publication Type :
- Academic Journal
- Accession number :
- 25800778
- Full Text :
- https://doi.org/10.1016/j.stem.2015.03.002