Dynamic epigenomic landscapes during early lineage specification in mouse embryos

Nat Genet. 2018 Jan;50(1):96-105. doi: 10.1038/s41588-017-0003-x. Epub 2017 Dec 4.

Abstract

In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes acting in concert with initial cell fate commitment remains poorly characterized. Here we report a comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele-specific and lineage-specific de novo methylation at CG and CH sites that led to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA-methylation valleys. By using Hi-C experiments to define chromatin architecture across the same developmental period, we demonstrated that both global demethylation and remethylation in early development correlate with chromatin compartments. Dynamic local methylation was evident during gastrulation, which enabled the identification of putative regulatory elements. Finally, we found that de novo methylation patterning does not strictly require implantation. These data reveal dynamic transcriptomes, DNA methylomes, and 3D chromatin landscapes during the earliest stages of mammalian lineage specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Blastocyst / metabolism
  • Cell Lineage / genetics
  • Chromatin / chemistry
  • DNA Methylation*
  • Embryo Implantation
  • Embryo, Mammalian / metabolism*
  • Endoderm / metabolism
  • Epigenesis, Genetic*
  • Gastrulation / genetics
  • Germ Layers / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Transcriptome

Substances

  • Chromatin