Dynamic epigenomic landscapes during early lineage specification in mouse embryos

In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes in concert with initial cell fate commitment remains poorly characterized. Here, we report comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele- and lineage-specific de novo methylation at CG and CH sites, leading to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA methylation valleys. By determining chromatin architecture using Hi-C across the same developmental period, we showed both global demethylation and remethylation in early development correlate with chromatin compartments. Dynamic local methylation is evident during gastrulation, which revealed maps of putative regulatory elements. Finally, we found that de novo methylation patterning does not strictly require implantation. These data unveiled dynamic transcriptomes, DNA methylomes, and 3D chromatin landscapes during the earliest mammalian lineage specification. Overall design: Mouse preimplantation, periimplantation and postimplantation embryos were obtained from crosses of C57BL/6N and DBA/2N as well as C57BL/6N and PWK/PhJ. STEM-seq, RNA-seq and Hi-C were performed in these embryos at various stages in development. STEM-seq was also performed on Tet1/2 double knockout embryos and in vitro culture embryos.