Developmental Epigenetics and Disease, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), 138673 Singapore,;
Genes Dev. 2014 Apr 15;28(8):812-28. doi: 10.1101/gad.234294.113.
Methylation of DNA is an essential epigenetic control mechanism in mammals. During embryonic development, cells are directed toward their future lineages, and DNA methylation poses a fundamental epigenetic barrier that guides and restricts differentiation and prevents regression into an undifferentiated state. DNA methylation also plays an important role in sex chromosome dosage compensation, the repression of retrotransposons that threaten genome integrity, the maintenance of genome stability, and the coordinated expression of imprinted genes. However, DNA methylation marks must be globally removed to allow for sexual reproduction and the adoption of the specialized, hypomethylated epigenome of the primordial germ cell and the preimplantation embryo. Recent technological advances in genome-wide DNA methylation analysis and the functional description of novel enzymatic DNA demethylation pathways have provided significant insights into the molecular processes that prepare the mammalian embryo for normal development.
DNA 甲基化是哺乳动物中一种重要的表观遗传调控机制。在胚胎发育过程中,细胞被引导向其未来的谱系,而 DNA 甲基化构成了一个基本的表观遗传障碍,指导和限制分化,并防止回归到未分化状态。DNA 甲基化在性染色体剂量补偿、抑制威胁基因组完整性的逆转座子、维持基因组稳定性以及印迹基因的协调表达中也起着重要作用。然而,为了进行有性繁殖,并采用原始生殖细胞和植入前胚胎的专门的、低甲基化的表观基因组,必须全局去除 DNA 甲基化标记。全基因组 DNA 甲基化分析和新型酶促 DNA 去甲基化途径的功能描述方面的最新技术进展,为我们理解哺乳动物胚胎为正常发育做准备的分子过程提供了重要的见解。