Allelic reprogramming of 3D chromatin architecture during early mammalian development
Allelic reprogramming of 3D chromatin architecture during early mammalian development
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早期哺乳动物发育过程中 3D 染色质结构的等位基因重编程
DOI：
10.1038/nature23263
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发表时间：
2017-07-13
期刊：
影响因子：
64.8
通讯作者：
Xie, Wei
中科院分区：
文献类型：
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作者：
Du, Zhenhai;Zheng, Hui;Xie, Wei
在哺乳动物中，受精后染色质组织经历了剧烈的重编程(1)。然而，染色质的三维结构及其在着床前发育中的重编程仍然知之甚少。在这里，通过开发一种低输入的Hi-C（全基因组染色体构象捕获）方法，我们研究了小鼠早期发育过程中染色质组织的重编程。我们发现卵母细胞在中期II表现出均匀的染色质折叠，缺乏可检测的拓扑相关结构域（TADs）和染色质室。引人注目的是，受精后染色质显示出大大减少的高阶结构。出乎意料的是，随后染色质组织的建立是一个延长的过程，贯穿着床前的发育，其特征是TADs的缓慢巩固和染色质室的分离。两组亲本染色体在空间上彼此分离，在受精卵中表现出明显的区隔化。这种等位基因分离和等位基因区隔现象可以在8细胞期发现。最后，我们表明着床前胚胎中的染色质压实可以部分地在没有合子转录的情况下进行，并且是一个多层次的分层过程。综上所述，我们的数据表明，受精后染色质可能处于一种明显放松的状态，随后在发育早期染色质结构逐渐成熟。
In mammals, chromatin organization undergoes drastic reprogramming after fertilization(1). However, the three-dimensional structure of chromatin and its reprogramming in preimplantation development remain poorly understood. Here, by developing a low-input Hi-C (genome-wide chromosome conformation capture) approach, we examined the reprogramming of chromatin organization during early development in mice. We found that oocytes in metaphase II show homogeneous chromatin folding that lacks detectable topologically associating domains (TADs) and chromatin compartments. Strikingly, chromatin shows greatly diminished higher-order structure after fertilization. Unexpectedly, the subsequent establishment of chromatin organization is a prolonged process that extends through preimplantation development, as characterized by slow consolidation of TADs and segregation of chromatin compartments. The two sets of parental chromosomes are spatially separated from each other and display distinct compartmentalization in zygotes. Such allele separation and allelic compartmentalization can be found as late as the 8-cell stage. Finally, we show that chromatin compaction in preimplantation embryos can partially proceed in the absence of zygotic transcription and is a multi-level hierarchical process. Taken together, our data suggest that chromatin may exist in a markedly relaxed state after fertilization, followed by progressive maturation of higher-order chromatin architecture during early development.