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

by Lei Liu, Guang Shi, D. Thirumalai, Changbong Hyeon

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 (≳O ( 10 2 ) 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.

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