Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing, China.
Biomedical Institute for Pioneering Investigation via Convergence and Center for Reproductive Medicine, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing, China.
Nat Genet. 2018 Jan;50(1):12-19. doi: 10.1038/s41588-017-0007-6. Epub 2017 Dec 18.
DNA methylation is a crucial layer of epigenetic regulation during mammalian embryonic development . Although the DNA methylome of early human embryos has been analyzed , 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.
DNA 甲基化是哺乳动物胚胎发育过程中表观遗传调控的关键层次。尽管已经分析了早期人类胚胎的 DNA 甲基组，但迄今为止仍未解决一些关键特征。在这里，我们对人类着床前胚胎进行了单细胞 DNA 甲基组测序，发现数以万计的基因组位点表现出从头 DNA 甲基化。这一发现表明，着床前发育过程中全基因组 DNA 甲基化重编程是强烈的全局去甲基化和剧烈的有针对性的再甲基化之间的动态平衡。此外，父本基因组的去甲基化速度比母本基因组快得多且彻底。从两细胞到着床后阶段，父本基因组的甲基化一直低于母本基因组。我们还表明，早期卵裂球的遗传谱系可以通过 DNA 甲基化分析来追踪。我们的工作为揭示早期人类胚胎中 DNA 甲基化重编程的秘密铺平了道路。
