Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
THU-PKU Center for Life Sciences, Tsinghua University, Beijing, China.
Nat Genet. 2018 Jan;50(1):96-105. doi: 10.1038/s41588-017-0003-x. Epub 2017 Dec 4.
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.
在哺乳动物中，所有的体节发育都起源于早期胚胎中的谱系分离。然而，与初始细胞命运决定协同作用的转录组和表观基因组的动态仍知之甚少。在这里，我们报告了对围植期和植后期小鼠胚胎中早期谱系的转录组和碱基分辨率甲基组的全面研究。我们发现 CG 和 CH 位点的等位基因特异性和谱系特异性从头甲基化导致谱系调控因子启动子、基因体和 DNA 甲基化谷中的胚胎和胚胎外谱系之间的差异甲基化。通过使用 Hi-C 实验来定义同一发育时期的染色质结构，我们证明了早期发育中的全局去甲基化和再甲基化与染色质区室相关。在原肠胚形成过程中，明显存在动态的局部甲基化，这使得鉴定潜在的调控元件成为可能。最后，我们发现从头甲基化模式的形成并不严格依赖于着床。这些数据揭示了哺乳动物谱系特化的最早阶段的动态转录组、DNA 甲基组和 3D 染色质景观。
