Current theoretical models fail to predict the topological complexity of the human genome.
Current theoretical models fail to predict the topological complexity of the human genome.
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DOI：
10.3389/fmolb.2015.00048
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发表时间：
2015
影响因子：
5
通讯作者：
Vazquez M
中科院分区：
文献类型：
--
作者：
Arsuaga J;Jayasinghe RG;Scharein RG;Segal MR;Stolz RH;Vazquez M
理解人类基因组的折叠是现代结构生物学的一个关键挑战。染色质构象捕获测定的出现（例如，Hi-C）彻底改变了染色体生物学，并为基因组的三维结构提供了新的见解。实验数据非常复杂，需要使用定量工具进行分析。有人认为，从Hi-C测定获得的数据与基因组的分形组织一致。分形球的一个关键特征是缺乏拓扑复杂性（打结或互连）。然而，拓扑复杂性的缺乏与高分子物理学的结果相矛盾，高分子物理学的结果表明，受限体积中长线性聚合物的缠结随着长度和体积的减小而迅速增加。在某些生物系统中，体内和体外试验支持这一说法。我们模拟打结的格子多边形限制在一个球体内，并证明他们的接触频率同意与人类的Hi-C数据。我们的结论是，人类基因组的拓扑结构的复杂性，不能从目前的Hi-C数据推断。
Understanding the folding of the human genome is a key challenge of modern structural biology. The emergence of chromatin conformation capture assays (e.g., Hi-C) has revolutionized chromosome biology and provided new insights into the three dimensional structure of the genome. The experimental data are highly complex and need to be analyzed with quantitative tools. It has been argued that the data obtained from Hi-C assays are consistent with a fractal organization of the genome. A key characteristic of the fractal globule is the lack of topological complexity (knotting or inter-linking). However, the absence of topological complexity contradicts results from polymer physics showing that the entanglement of long linear polymers in a confined volume increases rapidly with the length and with decreasing volume. In vivo and in vitro assays support this claim in some biological systems. We simulate knotted lattice polygons confined inside a sphere and demonstrate that their contact frequencies agree with the human Hi-C data. We conclude that the topological complexity of the human genome cannot be inferred from current Hi-C data.