The one-dimensional information of genomic DNA is hierarchically packed inside the eukaryotic cell nucleus and organized in a three-dimensional (3D) space. Genome-wide chromosome conformation capture (Hi-C) methods have uncovered the 3D genome organization and revealed multiscale chromatin domains of compartments and topologically associating domains (TADs). Moreover, single-nucleosome live-cell imaging experiments have revealed the dynamic organization of chromatin domains caused by stochastic thermal fluctuations. However, the mechanism underlying the dynamic regulation of such hierarchical and structural chromatin units within the microscale thermal medium remains unclear. Microrheology is a way to measure dynamic viscoelastic properties coupling between thermal microenvironment and mechanical response. Here, we propose a new, to our knowledge, microrheology for Hi-C data to analyze the dynamic compliance property as a measure of rigidness and flexibility of genomic regions along with the time evolution. Our method allows the conversion of an Hi-C matrix into the spectrum of the dynamic rheological property along the genomic coordinate of a single chromosome. To demonstrate the power of the technique, we analyzed Hi-C data during the neural differentiation of mouse embryonic stem cells. We found that TAD boundaries behave as more rigid nodes than the intra-TAD regions. The spectrum clearly shows the dynamic viscoelasticity of chromatin domain formation at different timescales. Furthermore, we characterized the appearance of synchronous and liquid-like intercompartment interactions in differentiated cells. Together, our microrheology data derived from Hi-C data provide physical insights into the dynamics of the 3D genome organization.

中文翻译：

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Hi-C 数据的微流变学揭示了动态 3D 基因组组织的光谱

基因组 DNA 的一维信息分层堆积在真核细胞核内，并组织在三维 (3D) 空间中。全基因组染色体构象捕获 (Hi-C) 方法揭示了 3D 基因组组织，并揭示了隔室和拓扑关联域 (TAD) 的多尺度染色质域。此外，单核小体活细胞成像实验揭示了由随机热波动引起的染色质域的动态组织。然而，在微型热介质中动态调节这种分层和结构染色质单元的机制仍不清楚。微流变学是一种测量热微环境与机械响应之间动态粘弹性耦合的方法。在这里，我们提出了一个新的，据我们所知，用于 Hi-C 数据的微流变学分析动态柔顺性，作为衡量基因组区域刚性和灵活性以及时间演化的指标。我们的方法允许将 Hi-C 矩阵转换为沿单个染色体基因组坐标的动态流变特性谱。为了证明该技术的威力，我们分析了小鼠胚胎干细胞神经分化过程中的 Hi-C 数据。我们发现 TAD 边界表现为比内部 TAD 区域更刚性的节点。该光谱清楚地显示了不同时间尺度染色质结构域形成的动态粘弹性。此外，我们表征了分化细胞中同步和类似液体的隔室间相互作用的出现。一起，