Dynamic epigenomic landscapes during early lineage specification in mouse embryos
Dynamic epigenomic landscapes during early lineage specification in mouse embryos
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DOI：
10.1038/s41588-017-0003-x
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发表时间：
2017-11
期刊：
影响因子：
30.8
通讯作者：
Yu Zhang-;Yunlong Xiang;Qiangzong Yin;Zhenhai Du;Xu Peng;Qiujun Wang;Miguel Fidalgo;Weikun Xia;
中科院分区：
文献类型：
--
作者：
Yu Zhang-;Yunlong Xiang;Qiangzong Yin;Zhenhai Du;Xu Peng;Qiujun Wang;Miguel Fidalgo;Weikun Xia;
在哺乳动物中，所有的体细胞发育都起源于早期胚胎的世系分离。然而，转录本和表观基因组与最初的细胞命运承诺相一致的动态仍然没有得到很好的描述。在这里，我们报告了一项关于移植前后小鼠胚胎早期谱系的转录本和碱基分辨甲基组的全面调查。我们在CG和CH位点发现了等位基因特异性和谱系特异性的从头甲基化，这导致了在谱系调节、基因体和DNA甲基化谷的启动子上胚胎和胚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重新甲基化都与染色质隔室相关。在原肠形成过程中，动态的局部甲基化是明显的，这使得能够识别假定的调控元件。最后，我们发现从头开始甲基化模式并不严格需要植入。这些数据揭示了哺乳动物谱系确定的早期阶段的动态转录本、DNA甲基组和3D染色质景观。
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.