Tata Institute of Fundamental Research, Hyderabad 500046, India.
Phys Rev E. 2022 Jun;105(6-1):064402. doi: 10.1103/PhysRevE.105.064402.
Underneath its apparently simple architecture, the circular chromosome of Escherichia coli is known for displaying complex dynamics in its cytoplasm, with past investigations hinting at inherently diverse mobilities of chromosomal loci across the genome. To decipher its origin, we simulate the dynamics of genome-wide spectrum of E. coli chromosomal loci, via integrating its experimentally derived Hi-C interaction matrix within a polymer-based model. Our analysis demonstrates that, while the dynamics of the chromosome is subdiffusive in a viscoelastic media, the diffusion constants are strongly dependent of chromosomal loci coordinates and diffusive exponents (α) are widely heterogenous with α ≈ 0.36-0.60. The loci-dependent heterogeneous dynamics and mean first-passage times of interloci encounter were found to be modulated via genetically distant interloci communications and is robust even in the presence of active, ATP-dependent noises. Control investigations reveal that the absence of Hi-C-derived interactions in the model would have abolished the traits of heterogeneous loci diffusion, underscoring the key role of loci-specific genetically distant interaction in modulating the underlying heterogeneity of the loci diffusion.
在其看似简单的结构之下,大肠杆菌的环状染色体以其在细胞质中呈现出复杂的动力学而闻名,过去的研究表明,基因组中染色体位置的固有移动性具有多样性。为了解其起源,我们通过在基于聚合物的模型中整合其经过实验得出的 Hi-C 相互作用矩阵,模拟了大肠杆菌全基因组范围内的染色体位置的动力学。我们的分析表明,虽然在粘弹性介质中染色体的动力学是亚扩散的,但扩散常数强烈依赖于染色体位置的坐标,并且扩散指数(α)具有广泛的异质性,α≈0.36-0.60。发现依赖于位置的异质动力学和位置间相遇的平均首次通过时间可以通过遗传上遥远的位置间通信进行调节,即使在存在活跃的、ATP 依赖性噪声的情况下也是如此。对照研究表明,如果模型中不存在由 Hi-C 产生的相互作用,那么异质位置扩散的特征就会被消除,这突显了位置特异性的遗传上遥远相互作用在调节位置扩散的潜在异质性方面的关键作用。