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人类间期染色体的链组织决定了染色质位置的时空动力学。

Chain organization of human interphase chromosome determines the spatiotemporal dynamics of chromatin loci.

机构信息

Korea Institute for Advanced Study, Seoul, Korea.

Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD, USA.

出版信息

PLoS Comput Biol. 2018 Dec 3;14(12):e1006617. doi: 10.1371/journal.pcbi.1006617. eCollection 2018 Dec.

Abstract

We investigate spatiotemporal dynamics of human interphase chromosomes by employing a heteropolymer model that incorporates the information of human chromosomes inferred from Hi-C data. Despite considerable heterogeneities in the chromosome structures generated from our model, chromatins are organized into crumpled globules with space-filling (SF) statistics characterized by a single universal scaling exponent (ν = 1/3), and this exponent alone can offer a quantitative account of experimentally observed, many different features of chromosome dynamics. The local chromosome structures, whose scale corresponds to that of topologically associated domains (∼ 0.1 - 1 Mb), display dynamics with a fast relaxation time (≲ 1 - 10 sec); in contrast, the long-range spatial reorganization of the entire chromatin ([Formula: see text] Mb) occurs on a much slower time scale (≳ hour), providing the dynamic basis of cell-to-cell variability and glass-like behavior of chromosomes. Biological activities, modeled using stronger isotropic white noises added to active loci, accelerate the relaxation dynamics of chromatin domains associated with the low frequency modes and induce phase segregation between the active and inactive loci. Surprisingly, however, they do not significantly change the dynamics at local scales from those obtained under passive conditions. Our study underscores the role of chain organization of chromosome in determining the spatiotemporal dynamics of chromatin loci.

摘要

我们通过采用一种包含从 Hi-C 数据推断出的人类染色体信息的杂多聚物模型来研究人类间期染色体的时空动力学。尽管我们的模型生成的染色体结构存在相当大的异质性,但染色质被组织成具有空间填充(SF)统计特征的皱缩球,其特征是单个通用标度指数(ν=1/3),并且这个指数本身可以定量描述实验观察到的许多不同的染色体动力学特征。局部染色体结构的尺度对应于拓扑相关域的尺度(约 0.1-1 Mb),其动力学具有快速松弛时间(≲1-10 秒);相比之下,整个染色质的长程空间重组([Formula: see text] Mb)发生在慢得多的时间尺度(≳小时),为细胞间变异性和染色体的玻璃状行为提供了动态基础。使用添加到活性位点的更强各向同性白噪声模拟的生物活性加速了与低频模式相关的染色质域的松弛动力学,并在活性和非活性位点之间诱导了相位分离。然而,令人惊讶的是,它们并没有从被动条件下获得的动力学显著改变局部尺度的动力学。我们的研究强调了染色体链组织在决定染色质位点时空动力学中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4650/6292649/9e6d57fdfb84/pcbi.1006617.g002.jpg

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