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.

中文翻译：

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小鼠胚胎早期谱系规范期间的动态表观基因组景观。

在哺乳动物中，所有体细胞发育都源于早期胚胎的谱系分离。然而，转录组和表观基因组与初始细胞命运承诺协同作用的动态仍然知之甚少。在这里，我们报告了对植入前后小鼠胚胎早期谱系的转录组和碱基分辨率甲基化组的全面研究。我们在 CG 和 CH 位点发现等位基因特异性和谱系特异性从头甲基化，导致胚胎谱系和胚胎外谱系在谱系调节子、基因体和 DNA 甲基化谷的启动子处出现差异甲基化。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整体去甲基化和再甲基化都与染色质区室相关。原肠胚形成过程中动态局部甲基化很明显，这使得能够识别假定的调控元件。最后，我们发现从头甲基化模式并不严格要求植入。这些数据揭示了哺乳动物谱系规范最早阶段的动态转录组、DNA 甲基化组和 3D 染色质景观。