Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Institute of Cell Biology, Center for Molecular Biology of Inflammation, University of Münster, Münster, 48149, Germany.
Nat Commun. 2019 Jul 11;10(1):3054. doi: 10.1038/s41467-019-10895-6.
Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. However, it is currently unclear how evolutionarily conserved these processes are. Here we characterise the DNA methylomes of zebrafish PGCs at four developmental stages and identify retention of paternal epigenetic memory, in stark contrast to the findings in mammals. Gene expression profiling of zebrafish PGCs at the same developmental stages revealed that the embryonic germline is defined by a small number of markers that display strong developmental stage-specificity and that are independent of DNA methylation-mediated regulation. We identified promoters that are specifically targeted by DNA methylation in somatic and germline tissues during vertebrate embryogenesis and that are frequently misregulated in human cancers. Together, these detailed methylome and transcriptome maps of the zebrafish germline provide insight into vertebrate DNA methylation reprogramming and enhance our understanding of the relationships between germline fate acquisition and oncogenesis.
哺乳动物胚胎发生过程中会发生两次 DNA 甲基化重编程；一次是在着床前发育过程中，另一次是在原始生殖细胞 (PGC) 形成过程中。然而，目前尚不清楚这些过程在进化上是如何保守的。在这里，我们描述了斑马鱼 PGC 在四个发育阶段的 DNA 甲基组，并鉴定出了保留的父系表观遗传记忆，这与哺乳动物的研究结果形成鲜明对比。在相同发育阶段对斑马鱼 PGC 的基因表达谱分析表明，胚胎生殖细胞由少数显示强烈发育阶段特异性且独立于 DNA 甲基化调控的标记定义。我们鉴定了在脊椎动物胚胎发生过程中，生殖细胞和体细胞组织中特异性靶向 DNA 甲基化的启动子，这些启动子在人类癌症中经常失调。这些详细的斑马鱼生殖系甲基组和转录组图谱共同提供了对脊椎动物 DNA 甲基化重编程的深入了解，并增强了我们对生殖系命运获得与肿瘤发生之间关系的理解。
