Dynamic epigenomic landscapes during early lineage specification in mouse embryos

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.

MOFA+: a probabilistic framework for comprehensive integration of structured single-cell data

“…MOFA+ links Factor 1 to changes across all molecular layers. Notably, the distribution of weights for DNA methylation are skewed towards negative values (at both enhancers and promoters), indicating that ExE endoderm cells are characterised by a state of global demethylation, consistent with previous studies 44 .…”

Long term effects of ART: What do animals tell us?

“…Paternal and maternal genomes brought into a common oocyte cytoplasm by fertilization are first de‐methylated, with different kinetics and by different molecular processes (Canovas et al, ; Salvaing et al, ). The methylation decreases during cleavages and thus over embryonic genome activation, and reaches its lowest level at the blastocyst stage (Guo et al, ; Zhang et al, ). Then de novo methylation occurs around implantation most extensively in the pluripotent epiblast (Smith et al, ) than in extraembryonic tissues where methylation remains lower than in the epiblast and future fetus (Oda, Oxley, Dean, & Reik, ).…”

Molecular characterization of DNA methyltransferase 1 and its role in temperature change of armyworm Mythimna separata Walker

“…Dnmt1 contains three isoforms, Dnmt1o, Dnmt1s , and Dnmt1 , and is considered to be responsible for the maintenance of methylation (Auclair & Weber, 2012); Dnmt2 shows weak DNA methylation activity and is involved in transfer RNA methylation (Tatematsu, Yamazaki, & Ishikawa, 2000); in contrast, the Dnmt3 family includes Dnmt3a and Dnmt3b , which participate in de novo methylation, and are therefore considered de novo methyltransferases (Auclair & Weber, 2012). The de novo methyltransferases Dnmt3a and Dnmt3b are all essential for genome regulation and mammalian development (Jin et al, 2018; Steffen et al, 2018; Zhang et al, 2018). In contrast to mammals, some insects, including the silkworm Bombyx mori and the locusts Schistocerca gregaria and Tribolium castaneum , may only have Dnmt1 and Dnmt2 , indicating that Dnmt1 may play a role in maintaining methylation and de novo methylation (Glastad, Hunt, Yi, & Goodisman, 2011; Lyko & Maleszka, 2011).…”