3月28日，哈佛-麻省理工博德研究所的Alexander Meissner等人在Nature在線發(fā)表了一篇名為“A unique regulatory phase of DNA methylation in the early mammalian embryo”的文章，闡明了哺乳動(dòng)物胚胎早期一種獨(dú)特的DNA甲基化模型。
DNA甲基化是高度活躍于哺乳動(dòng)物胚胎形成期,。
總所周知,，父源基因組在受精時(shí)通過(guò)甲基化胞嘧啶被積極的失活，隨后，在囊胚期達(dá)到最低,。
然而，這種模型是基于有限的數(shù)據(jù)而來(lái),，到目前為止,，沒(méi)有存在的單堿基分辨率的圖譜來(lái)支持和完善這個(gè)模型。這里,，研究人員根據(jù)老鼠配子及移植后的受精卵得到了基因組規(guī)模的DNA甲基化圖譜,。
結(jié)果發(fā)現(xiàn)，卵母細(xì)胞確實(shí)表現(xiàn)出全基因組的低甲基化,，尤其是在一些特殊家族如長(zhǎng)散布元件1和以及長(zhǎng)末端重復(fù)的逆轉(zhuǎn)錄元件,，它們?cè)谂渥雍褪芫讯急徊煌募谆?/p>
令人吃驚的是，卵母細(xì)胞提供了一套獨(dú)特的區(qū)別性甲基化區(qū)域(DMRs)包括許多CpG島啟動(dòng)子,，它們?cè)谠缙谂咛ブ芯S持存在,，卻在體細(xì)胞中丟失。
與此相反,，精子提供的DMRs主要在基因間,，在胚泡時(shí)期后被高度甲基化。
胚胎時(shí)期是表觀遺傳修飾最活躍的時(shí)期,，這項(xiàng)研究正利用在預(yù)先指定的胚胎,，得到了一個(gè)基因組規(guī)模的，單堿基分辨率時(shí)間線的DNA甲基化圖譜,。（生物谷Deepblue編譯）
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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