Toward understanding the dynamic state of 3D genome
Toward understanding the dynamic state of 3D genome
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DOI：
10.1016/j.csbj.2020.08.014
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发表时间：
2020-01-01
影响因子：
6
通讯作者：
Nakato, Ryuichiro
中科院分区：
文献类型：
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作者：
Shinkai, Soya;Onami, Shuichi;Nakato, Ryuichiro
在细胞生物学领域，三维基因组组织及其在生物学活动中的作用已经被研究了十多年。最近利用活体成像和聚合物模拟的研究表明，高阶染色质结构是动态的；基于整体的染色体构象捕获技术(Hi-C)无法捕捉到核小体和基因组位置的随机波动。在这篇综述中，我们关注3D基因组结构的物理性质。我们首先描述了如何使用聚合物建模来解码海量Hi-C数据。然后，我们介绍了我们最近开发的Phi-C方法，这是一个在随机热噪声存在的情况下模拟3D基因组组织涨落的计算工具。我们还提出了另一种分析动态流变性(表示为微观流变学光谱)的新方法，作为基因组区域随时间变化的灵活性和刚性的衡量标准。通过将这些方法应用于真实的Hi-C数据，我们突出了嵌入在3D基因组组织中的时间层次；染色质相互作用的边界比边界内部更严格，而功能域在特定的时间间隔内以动态波动的形式出现。我们的方法可能会弥合活细胞成像和Hi-C数据之间的差距，并阐明动态3D基因组组织的本质。(C)2020年提交人(S)。由Elsevier B.V.代表计算和结构生物技术研究网络出版。
The three-dimensional (3D) genome organization and its role in biological activities have been investigated for over a decade in the field of cell biology. Recent studies using live-imaging and polymer simulation have suggested that the higher-order chromatin structures are dynamic; the stochastic fluctuations of nucleosomes and genomic loci cannot be captured by bulk-based chromosome conformation capture techniques (Hi-C). In this review, we focus on the physical nature of the 3D genome architecture. We first describe how to decode bulk Hi-C data with polymer modeling. We then introduce our recently developed PHi-C method, a computational tool for modeling the fluctuations of the 3D genome organization in the presence of stochastic thermal noise. We also present another new method that analyzes the dynamic rheology property (represented as microrheology spectra) as a measure of the flexibility and rigidity of genomic regions over time. By applying these methods to real Hi-C data, we highlighted a temporal hierarchy embedded in the 3D genome organization; chromatin interaction boundaries are more rigid than the boundary interior, while functional domains emerge as dynamic fluctuations within a particular time interval. Our methods may bridge the gap between live-cell imaging and Hi-C data and elucidate the nature of the dynamic 3D genome organization. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.