3月28日,哈佛-麻省理工博德研究所的Alexander Meissner等人在Nature在线发表了一篇名为“A unique regulatory phase of DNA methylation in the early mammalian embryo”的文章,阐明了哺乳动物胚胎早期一种独特的DNA甲基化模型。
DNA甲基化是高度活跃于哺乳动物胚胎形成期。
总所周知,父源基因组在受精时通过甲基化胞嘧啶被积极的失活,随后,在囊胚期达到最低。
然而,这种模型是基于有限的数据而来,到目前为止,没有存在的单碱基分辨率的图谱来支持和完善这个模型。这里,研究人员根据老鼠配子及移植后的受精卵得到了基因组规模的DNA甲基化图谱。
结果发现,卵母细胞确实表现出全基因组的低甲基化,尤其是在一些特殊家族如长散布元件1和以及长末端重复的逆转录元件,它们在配子和受精卵都被不同的甲基化。
令人吃惊的是,卵母细胞提供了一套独特的区别性甲基化区域(DMRs)包括许多CpG岛启动子,它们在早期胚胎中维持存在,却在体细胞中丢失。
与此相反,精子提供的DMRs主要在基因间,在胚泡时期后被高度甲基化。
胚胎时期是表观遗传修饰最活跃的时期,这项研究正利用在预先指定的胚胎,得到了一个基因组规模的,单碱基分辨率时间线的DNA甲基化图谱。(生物谷Deepblue编译)
doi: 10.1038/nature10960
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PMID:
A unique regulatory phase of DNA methylation in the early mammalian embryo
Zachary D. Smith, Michelle M. Chan, Tarjei S. Mikkelsen, Hongcang Gu, Andreas Gnirke, Aviv Regev & Alexander Meissner
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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