Role of Tet3 and DNA replication in zygotic demethylation of both paternal and maternal genomes [RNA-seq]

With the exception of imprinted genes and certain repeats, DNA methylation is globally erased during pre-implantation development. Recent studies have suggested that Tet3-mediated oxidation of 5-methylcytosine (5mC) and DNA replication-dependent dilution both contribute to global paternal DNA demethylation, but demethylation of the maternal genome occurs via replication. Here we present genome-scale DNA methylation maps for both the paternal and maternal genomes of Tet3-depleted and/or DNA replication-inhibited zygotes. In both genomes, we found that inhibition of DNA replication blocks DNA demethylation independently from Tet3 function, and that Tet3 facilitates DNA demethylation by coupling with DNA replication. For both, our data indicate that replication-dependent dilution is the major contributor to demethylation, but Tet3 plays an important role, particularly at certain loci. Our study therefore both defines the respective functions of Tet3 and DNA replication in paternal DNA demethylation and reveals an unexpected contribution of Tet3 to demethylation of the maternal genome. In this data set, we include RNA-Seq data of mouse 2-cell embryos and blastocysts derived from both wildtype and Tet3-null oocytes除印记基因与特定重复序列外，DNA甲基化会在植入前发育过程中发生全局性清除。既往研究表明，Tet3介导的5-甲基胞嘧啶（5-methylcytosine, 5mC）氧化与依赖DNA复制的稀释效应共同参与父本基因组的全局性去甲基化过程，而母本基因组的去甲基化仅通过复制途径完成。本研究提供了Tet3缺陷或DNA复制受抑制的受精卵的父本与母本基因组的全基因组DNA甲基化图谱。研究发现，在两类基因组中，抑制DNA复制均可独立于Tet3功能阻断去甲基化过程，且Tet3可通过与DNA复制协同作用促进去甲基化。数据表明，依赖复制的稀释效应仍是去甲基化的主要驱动因素，但Tet3也发挥了重要作用，尤其在特定基因座处。因此，本研究既明确了Tet3与DNA复制在父本基因组去甲基化过程中的各自功能，同时也揭示了Tet3对母本基因组去甲基化的意外贡献。本数据集包含野生型与Tet3敲除小鼠卵母细胞所产生的2-细胞胚胎及囊胚的RNA测序（RNA-Seq）数据。