Hi-C embedded polymer model of Escherichia coli reveals the origin of heterogeneous subdiffusion in chromosomal loci

Abstract

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.