标题： 静态三维结构在间期染色体远端位点对之间的快速动力学中起决定性作用 显示英文标题

标题： Static Three-Dimensional Structures Determine Fast Dynamics Between Distal Loci Pairs in Interphase Chromosomes

摘要： 活细胞成像实验表明，尽管真核染色体是紧凑的，增强子和启动子之间的远端动力学出人意料地迅速，无法用标准聚合物模型来解释。 紧密的静态染色质组织（结构）与松弛时间（动力学）之间的不一致是一个悖论，违反了预期的结构-功能关系。 为了解决这个谜题，我们开发了一种理论，通过首先使用静态Hi-C接触图或固定细胞成像数据计算准确的三维（3D）结构来预测染色质动力学。 计算得到的三维坐标被用来准确预测最近实验中同时监测染色质动力学和转录的两点动力学。 值得注意的是，该理论不仅预测了观察到的快速增强子-启动子动力学，还揭示了两点松弛时间和基因组分离之间的新型标度关系，这与最近的实验结果非常接近。 该理论还预测，粘连蛋白耗尽会加速远端位点之间的动力学。 间期染色体中远端位点对的快速动力学以及粘连蛋白耗尽后染色质位点扩散的加速，都可以用图论中的基于结构的中心性度量来解释。 我们的框架表明，仅凭静态实验数据就可以预测染色质动力学，从而强化了三维结构决定其动态行为的概念。 该理论的普遍性为在不同生物背景下探索染色质动力学，尤其是转录动力学开辟了新的途径。 显示英文摘要

摘要： Live cell imaging experiments have shown that, although eukaryotic chromosomes are compact, the distal dynamics between enhancers and promoters are unexpectedly rapid and cannot be explained by standard polymer models. The discordance between the compact static chromatin organization (structure) and the relaxation times (dynamics) is a conundrum that violates the expected structure-function relationship. To resolve the puzzle, we developed a theory to predict chromatin dynamics by first calculating the accurate three-dimensional (3D) structure using static Hi-C contact maps or fixed-cell imaging data. The calculated 3D coordinates are used to accurately forecast the two-point dynamics reported in recent experiments that simultaneously monitor chromatin dynamics and transcription. Strikingly, the theory not only predicts the observed fast enhancer-promoter dynamics but also reveals a novel scaling relationship between two-point relaxation time and genomic separation that is in near quantitative agreement with recent experiments. The theory also predicts that cohesin depletion speeds up the dynamics between distal loci. Both the rapid dynamics between distal loci pairs in interphase chromosomes and the acceleration of chromatin loci diffusion upon cohesin depletion are explained in terms of structure-based centrality measure used in graph theory. Our framework shows that chromatin dynamics can be predicted based solely on static experimental data, reinforcing the concept that the three-dimensional structure determines their dynamic behavior. The generality of the theory opens new avenues for exploring chromatin dynamics, especially transcriptional dynamics, across different biological contexts.