Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity
Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity
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DOI：
10.1038/s41467-020-16919-w
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发表时间：
2020-06-19
影响因子：
16.6
通讯作者：
Weber, Michael
中科院分区：
文献类型：
--
作者：
Dahlet, Thomas;Argueso Lleida, Andrea;Weber, Michael
小鼠胚胎在植入过程中获得其基因组的整体DNA甲基化。然而，DNA甲基转移酶（DNMTs）在胚胎中的确切作用尚未得到全面研究。本文系统分析了Dnmt 1、Dnmt 3a和Dnmt 3b基因失活对小鼠胚胎甲基化组和转录组的影响。我们发现DNMT 1（负责维持甲基化）和DNMT 3A/B（仅负责发育中的甲基化获得）之间的功能有严格的分工。通过分析严重低甲基化的胚胎，我们发现了DNA甲基化的多种功能，这些功能被用作一组基因的抑制机制，这些基因不仅包括印记基因和种系基因，还包括谱系定型基因和2细胞基因。DNA甲基化还抑制多个反转录转座子和来自转座子和基因体中隐蔽启动子的非法转录物。我们的工作提供了DNA甲基转移酶的作用和DNA甲基化对哺乳动物胚胎转录组完整性的重要性的全面分析。DNA甲基转移酶在小鼠胚胎发育过程中起重要作用。在这里，作者揭示了Dnmt 1，Dnmt 3a和Dnmt 3b基因失活对小鼠胚胎全基因组甲基化组和转录组的影响。
Mouse embryos acquire global DNA methylation of their genome during implantation. However the exact roles of DNA methyltransferases (DNMTs) in embryos have not been studied comprehensively. Here we systematically analyze the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos. We find a strict division of function between DNMT1, responsible for maintenance methylation, and DNMT3A/B, solely responsible for methylation acquisition in development. By analyzing severely hypomethylated embryos, we uncover multiple functions of DNA methylation that is used as a mechanism of repression for a panel of genes including not only imprinted and germline genes, but also lineage-committed genes and 2-cell genes. DNA methylation also suppresses multiple retrotransposons and illegitimate transcripts from cryptic promoters in transposons and gene bodies. Our work provides a thorough analysis of the roles of DNA methyltransferases and the importance of DNA methylation for transcriptome integrity in mammalian embryos. DNA methyltrasferases play important role during mouse embryo development. Here the authors reveal the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos genome-wide.