【原】哺乳动物早期胚胎中DNA甲基化的一个独特的调节期

A unique regulatory phase of DNA methylation in the early mammalian embryo

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|核心内容：

在哺乳动物胚胎发育过程中，DNA甲基化是高度动态的。人们普遍认为，父源的基因组在受精时主动清除5-甲基胞嘧啶上的甲基，随后的是母源和父源基因组的被动去甲基化，甲基化在囊胚阶段达到最小。

然而，支持该模型的数据太有限。到目前为止，还没有碱基分辨率的图谱来支持和更精确地描述它。

在这里，我们绘制了小鼠生殖细胞基因组从受精前到植入后整个过程的基因组规模的DNA甲基化图谱。

我们发现卵母细胞已经表现出整体的低甲基化，特别是在特定的长散布元件1和长末端重复反转录元件家族中，这些元件在配子之间的甲基化程度不同，导致受精卵中的甲基化处于非常低的程度。

令人惊讶的是，卵母细胞贡献了一组独特的差异甲基化区域（Differentially Methylated Regions，DMRs)——包括许多CpG岛启动子——这些区域在早期胚胎中保持不变，但一旦分化就会逐渐丢失，并且在体细胞中消失。相比之下，精子贡献的 DMRs 在很大程度上是基因间的（介于两个基因序列之间），且在囊胚阶段之后变得高度甲基化。我们的数据提供了细胞命运决定（原肠运动）之前的胚胎中基因组规模碱基分辨率的DNA甲基化图谱。

不同来源基因组甲基化变化规律

英文摘要：

DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)--including many CpG island promoters--that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.

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参考文献：

http:///backend/ptpmcrender.fcgi?accid=PMC3331945&blobtype=pdf