Enhancer hubs and loop collisions identified from single-allele topologies
Enhancer hubs and loop collisions identified from single-allele topologies
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DOI：
10.1038/s41588-018-0161-5
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发表时间：
2018-08-01
期刊：
影响因子：
30.8
通讯作者：
de Laat, Wouter
中科院分区：
文献类型：
--
作者：
Allahyar, Amin;Vermeulen, Carlo;de Laat, Wouter
染色质折叠有助于调节基因组过程，如基因活性。现有的构象捕获方法通过分析细胞群体中成对的染色质接触来表征基因组拓扑结构，但不能辨别个体相互作用是同时发生还是竞争性发生。在这里，我们提出了多接触4C（MC-4C），它应用纳米孔测序来研究单个等位基因的多路DNA构象。MC-4C区分合作与随机和竞争相互作用，并识别细胞亚群中以前丢失的结构。我们发现，β-珠蛋白超增强子的单个元素可以聚集成一个增强子中心，可以同时容纳两个基因。相邻的染色质结构域环可以通过它们的CTCF结合锚的碰撞形成玫瑰花状结构，如在缺乏粘附素卸载因子WAPL的细胞中最显著地看到的。在这里，CTCF锚定的染色质环的大规模碰撞被认为反映了“粘附素交通堵塞”。因此，单等位基因拓扑学研究有助于我们理解基因组折叠和功能的潜在机制。
Chromatin folding contributes to the regulation of genomic processes such as gene activity. Existing conformation capture methods characterize genome topology through analysis of pairwise chromatin contacts in populations of cells but cannot discern whether individual interactions occur simultaneously or competitively. Here we present multi-contact 4C (MC-4C), which applies Nanopore sequencing to study multi-way DNA conformations of individual alleles. MC-4C distinguishes cooperative from random and competing interactions and identifies previously missed structures in subpopulations of cells. We show that individual elements of the beta-globin superenhancer can aggregate into an enhancer hub that can simultaneously accommodate two genes. Neighboring chromatin domain loops can form rosette-like structures through collision of their CTCF-bound anchors, as seen most prominently in cells lacking the cohesin-unloading factor WAPL. Here, massive collision of CTCF-anchored chromatin loops is believed to reflect 'cohesin traffic jams'. Single-allele topology studies thus help us understand the mechanisms underlying genome folding and functioning.