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bioRxiv · 10.1101/223669

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

Liu, L.·Shi, G.·Thirumalai, D.·Hyeon, C.
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Abstract

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 ({nu} = 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 ([lsim] 50 sec), whereas the long-range spatial reorganization of the entire chromatin [Formula] occurs on a much longer time scale ({gtrsim} 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.\n\nSignificance StatementChromosomes are giant chain molecules made of hundreds of megabase-long DNA intercalated with proteins. Structure and dynamics of interphase chromatin in space and time hold the key to understanding the cell type-dependent gene regulation. In this study, we establish that the crumpled and space-filling organization of chromatin fiber in the chromosome territory, characterized by a single universal exponent used to describe polymer sizes, is sufficient to explain the complex spatiotemporal hierarchy in chromatin dynamics as well as the subdiffusive motion of the chromatin loci. While seemingly a daunting problem at a first glance, our study shows that relatively simple principles, rooted in polymer physics, can be used to grasp the essence of dynamical properties of the interphase chromatin.

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Liu, L., Shi, G., Thirumalai, D., Hyeon, C.. 2017-11-22. Architecture of human interphase chromosome determines the spatiotemporal dynamics of chromatin loci. https://doi.org/10.1101/223669

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