Abstract
DNA methylation plays important roles during development. However, the DNA methylation reprogramming of functional elements has not been fully investigated during mammalian embryonic development. Herein, using our modified MethylC-Seq library generation method and published post-bisulphite adapter-tagging (PBAT) method, we generated genome-wide DNA methylomes of human gametes and early embryos at single-base resolution and compared them with mouse methylomes. We showed that the dynamics of DNA methylation in functional elements are conserved between humans and mice during early embryogenesis, except for satellite repeats. We further found that oocyte-specific hypomethylated promoters usually exhibit low CpG densities. Genes with oocyte-specific hypomethylated promoters generally show oocyte-specific hypomethylated genic and intergenic regions, and these hypomethylated regions contribute to the hypomethylation pattern of mammalian oocytes. Furthermore, hypomethylated genic regions with low CG densities correlate with gene silencing in oocytes, whereas hypomethylated genic regions with high CG densities correspond to high gene expression. We further show that methylation reprogramming of enhancers during early embryogenesis is highly associated with the development of almost all human organs. Our data support the hypothesis that DNA methylation plays important roles during mammalian development.
Highlights
Epigenetic information plays critical roles during animal development[1,2,3,4]
When we investigated the global dynamics of DNA methylomes during human early embryogenesis, our data showed that methylation levels declined from 0.61 to 0.30 during embryogenesis (Fig. 1a)
The results indicated that hypermethylated promoters correlated with low gene expression in embryos, while hypomethylated genic regions with a low CG density, correlated with gene silencing in oocytes
Summary
Epigenetic information plays critical roles during animal development[1,2,3,4]. The plasticity of the epigenome enables key epigenetic modification found in most plants, animals and fungal models is 5mC5, which has a profound impact on genome stability, gene expression and development[6,7,8].cell differentiation, organogenesis and animal develop- Recent studies have shown that the sperm DNA ment. Epigenetic information plays critical roles during animal development[1,2,3,4]. The plasticity of the epigenome enables key epigenetic modification found in most plants, animals and fungal models is 5mC5, which has a profound impact on genome stability, gene expression and development[6,7,8]. Cell differentiation, organogenesis and animal develop- Recent studies have shown that the sperm DNA ment. Proper epigenomic patterns are required to methylome can be stably inherited by early embryos in ensure the totipotency of early embryos of animals[2]. One zebrafish[9,10], indicating the existence of transgenerational epigenetic inheritance in animals. DNA demethylation occurs during early embryogenesis in both humans[11,12] and mice[12,13].
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