DNA methylation is a crucial layer of epigenetic regulation during mammalian embryonic development ^1-3 . Although the DNA methylome of early human embryos has been analyzed ^4-6 , some of the key features have not been addressed thus far. Here we performed single-cell DNA methylome sequencing for human preimplantation embryos and found that tens of thousands of genomic loci exhibited de novo DNA methylation. This finding indicates that genome-wide DNA methylation reprogramming during preimplantation development is a dynamic balance between strong global demethylation and drastic focused remethylation. Furthermore, demethylation of the paternal genome is much faster and thorough than that of the maternal genome. From the two-cell to the postimplantation stage, methylation of the paternal genome is consistently lower than that of the maternal genome. We also show that the genetic lineage of early blastomeres can be traced by DNA methylation analysis. Our work paves the way for deciphering the secrets of DNA methylation reprogramming in early human embryos.

中文翻译：

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人类植入前胚胎的单细胞DNA甲基化测序。

DNA甲基化是哺乳动物胚胎发育^1-3期间表观遗传调控的关键层。尽管已经分析了早期人类胚胎的DNA甲基化组^4-6，到目前为止，一些关键功能尚未得到解决。在这里，我们对人类植入前的胚胎进行了单细胞DNA甲基化测序，发现成千上万的基因组位点表现出从头DNA甲基化。这一发现表明，植入前发育过程中全基因组DNA甲基化重编程是强大的整体去甲基化与剧烈聚焦的再甲基化之间的动态平衡。此外，父本基因组的脱甲基比母本基因组的脱甲基要快得多。从两细胞到植入后阶段，父本基因组的甲基化始终低于母本基因组的甲基化。我们还表明，可以通过DNA甲基化分析来追溯早期卵裂球的遗传谱系。