DNA hydroxymethylome in mouse germline cells

In mammals, DNA 5-hydroxymethylcytosine is implicated in DNA methylation reprogramming during mouse early embryos development. However, the extent of 5hmC in participating in genome-wide methylation reprogramming remains largely unknown, due to the still lack of base resolution map of this modification in early embryos. Here, we illustrated landscapes of 5hmC in mouse preimplantation embryos, post implantation epiblast, primordial germ cells and gametes, thus providing detailed analysis across key developmental stages. In addition, the dynamics of 5hmC were tracked through parental-allele specific manner, which painted the differences in genome-wide 5hmC between maternal and paternal genomes. By combination with mouse models and chemical approaches, factors that influenced the characteristics of genomic 5hmC were further evaluated. In summary, our work provides invaluable resources and insights for the study of epigenetic regulation in development.在哺乳动物中，DNA 5-羟甲基胞嘧啶（5-hydroxymethylcytosine）参与小鼠早期胚胎发育过程中的DNA甲基化重编程（DNA methylation reprogramming）。然而，由于目前仍缺乏该修饰在早期胚胎中的碱基分辨率图谱（base resolution map），5hmC参与全基因组甲基化重编程的具体程度仍知之甚少。本研究绘制了小鼠着床前胚胎（preimplantation embryos）、着床后上胚层（post implantation epiblast）、原始生殖细胞（primordial germ cells）以及配子（gametes）中的5hmC修饰图谱，从而实现了关键发育阶段的精细化分析。此外，我们以亲本等位基因特异性（parental-allele specific）的方式追踪了5hmC的动态变化，揭示了母本与父本基因组间的全基因组5hmC差异。通过结合小鼠模型与化学干预手段，本研究进一步解析了影响基因组5hmC特征的调控因子。综上，本研究为发育过程中的表观遗传调控（epigenetic regulation）研究提供了极具价值的资源与理论见解。