DNA methylation dynamics of the human preimplantation embryo.
DNA methylation dynamics of the human preimplantation embryo.
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DOI：
10.1038/nature13581
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发表时间：
2014-07-31
期刊：
影响因子：
64.8
通讯作者：
Meissner, Alexander
中科院分区：
文献类型：
--
作者：
Smith, Zachary D.;Chan, Michelle M.;Humm, Kathryn C.;Karnik, Rahul;Mekhoubad, Shila;Regev, Aviv;Eggan, Kevin;Meissner, Alexander
在哺乳动物中，胞嘧啶甲基化主要限于CpG二核苷酸，并稳定地分布在整个基因组中，具有由DNA结合因子指导的局部细胞类型特异性调节。这种相对静止的景观与受精事件形成鲜明对比，在受精过程中，父亲的基因组被全球重新编程。父本基因组去甲基化包括大部分CpG，尽管甲基化在几个显著特征中保持。虽然这些动态已被广泛的特点，在小鼠中，只有有限的观察可在其他哺乳动物，并需要直接测量，以了解在何种程度上早期胚胎景观保存。我们提出了人类植入前发育和胚胎干细胞（ESC）衍生的基因组规模的DNA甲基化图谱，证实了包括大多数CpG在内的全球低甲基化的短暂状态，而持久维持的位点主要限于基因体。虽然大多数特征与小鼠具有相似的动力学，但母体贡献的甲基化被发散地靶向延伸超出已知印记控制区（ICR）的CpG岛（CGI）启动子的物种特异性集合。反转录转座子调节也是高度多样的，并且从母体向胚胎表达的物种特异性元件过渡。总之，我们的数据证实，父系基因组去甲基化是早期哺乳动物发育的一个普遍属性，其特征在于不同的表观遗传调控模式。
In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell type-specific regulation directed by DNA binding factors. This comparatively static landscape dramatically contrasts the events of fertilization, where the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, though methylation is maintained at several notable features. While these dynamics have been extensively characterized in the mouse, only limited observations are available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell (ESC) derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of persistent maintenance are primarily restricted to gene bodies. While most features share similar dynamics to mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island (CGI) promoters that extend beyond known Imprint Control Regions (ICRs). Retrotransposon regulation is also highly diverse and transitions from maternally to embryonically expressed, species-specific elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation.
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影响因子：
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作者：
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