Maternal DNA methylation regulates early trophoblast development

Critical roles for DNA methylation in embryonic development are well established, but less is known about the roles of DNA methylation during trophoblast development, the extraembryonic lineage that gives rise to the placenta. Here we dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b-null trophoblast. We find that most gene deregulation is explained by an erasure of maternal methylation in the oocyte, but partially independent of loss of imprinting of the trophoblast-essential Ascl2 gene. Our results reveal that maternal DNA methylation controls multiple differentiation and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. mRNA-seq and WGBS-seq of maternal Dnmt3a/3b-null trophoblast; mRNA-seq of maternal Ascl2 KO trophoblastDNA甲基化（DNA methylation）在胚胎发育中的关键作用已得到充分证实，但人们对其在滋养层（trophoblast）发育过程中的作用尚缺乏足够认知——滋养层是形成胎盘的胚外谱系。本研究通过对DNMT3a/3b缺失（Dnmt3a/3b-null）的滋养层细胞开展mRNA表达谱与DNA甲基化谱分析，解析了DNA甲基化在滋养层发育中的调控作用。研究发现，绝大多数基因表达失调可归因于卵母细胞内母本DNA甲基化的擦除，但该现象与滋养层核心必需基因Ascl2的印记丢失存在部分独立关联。本研究结果表明，母本DNA甲基化可通过印记依赖与非依赖两种调控机制，参与滋养层内多种分化与生理过程的调控。本数据集包含：母本DNMT3a/3b缺失滋养层细胞的mRNA测序（mRNA-seq）与全基因组亚硫酸氢盐测序（WGBS-seq）数据；母本Ascl2敲除（KO）滋养层细胞的mRNA测序（mRNA-seq）数据。