期刊
NATURE GENETICS
卷 50, 期 1, 页码 96-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41588-017-0003-x
关键词
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资金
- National Key R&D Program of China [2016YFC0900301, 2017YFC1001401]
- National Basic Research Program of China [2015CB856201]
- National Natural Science Foundation of China [31422031]
- THU-PKU Center for Life Sciences
- Beijing Advanced Innovation Center for Structural Biology
- Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore
- NIH [R01GM095942, R21HD087722]
- New York State Department of Health (NYSTEM) [C028103, C028121]
- Irma T. Hirschl and Weill-Caulier Trusts Career Scientist Award
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.
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