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Architecture of human interphase chromosome determines the spatiotemporal dynamics of chromatin loci

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

Posted 22 Nov 2017
bioRxiv DOI: 10.1101/223669 (published DOI: 10.1371/journal.pcbi.1006617)

By incorporating the information of human chromosome inferred from Hi-C experiments into a heteropolymer model of chromatin chain, we generate a conformational ensemble to investigate its spatiotemporal dynamics. The heterogeneous loci interactions result in hierarchical organization of chromatin chain, which obeys compact space-filling (SF) statistics at intermediate length scale. Remarkably, the higher order architecture of the chromatin, characterized by the single universal Flory exponent (ν=1/3) for condensed homopolymers, provides quantitative account of the dynamical properties of the chromosome. The local chromosome structures, exemplified by topologically associated domains (~ 0.1-1 Mb), display dynamics with fast relaxation time (≤ 50 sec), whereas the long-range spatial reorganization of the entire chromatin (≥ O(102) Mb) occurs on a much longer time scale (≥ hour), suggestive of glass-like behavior. This key finding provides the dynamic basis of cell-to-cell variability. Active forces, modeled using stronger isotropic white noises, accelerate the relaxation dynamics of chromatin domain described by the low frequency modes. Surprisingly, they do not significantly change the local scale dynamics from those under passive condition. By linking the spatiotemporal dynamics of chromosome with its organization, our study highlights the importance of physical constraints in chromosome architecture on the sluggish dynamics.

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