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Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development

机译:在小鼠植入前发育过程中建立染色质调节景观

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How the chromatin regulatory landscape in the inner cell mass cells is established from differentially packaged sperm and egg genomes during preimplantation development is unknown. Here, we develop a low-input DNase I sequencing (liDNase-seq) method that allows us to generate maps of DNase I-hypersensitive site (DHS) of mouse preimplantation embryos from 1-cell to morula stage. The DHS landscape is progressively established with a drastic increase at the 8-cell stage. Paternal chromatin accessibility is quickly reprogrammed after fertilization to the level similar to maternal chromatin, while imprinted genes exhibit allelic accessibility bias. We demonstrate that transcription factor Nfya contributes to zygotic genome activation and DHS formation at the 2-cell stage and that Oct4 contributes to the DHSs gained at the 8-cell stage. Our study reveals the dynamic chromatin regulatory landscape during early development and identifies key transcription factors important for DHS establishment in mammalian embryos.
机译:尚不清楚如何在植入前发育过程中从包装不同的精子和卵基因组建立内部细胞团细胞中的染色质调节景观。在这里,我们开发了一种低输入DNase I测序(liDNase-seq)方法,该方法使我们能够生成从1细胞到桑ula虫阶段的小鼠植入前胚胎的DNase I超敏感位点(DHS)的图。在8单元阶段,DHS格局逐步建立并急剧增加。父本染色质可及性在受精后迅速重新编程至与母本染色质相似的水平,而印迹基因显示等位基因可及性偏倚。我们证明,转录因子Nfya有助于2细胞阶段的合子基因组激活和DHS形成,并且Oct4有助于8细胞阶段获得的DHS。我们的研究揭示了早期发育过程中动态的染色质调控环境,并确定了对哺乳动物胚胎中DHS建立起重要作用的关键转录因子。

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