Abstract
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 ( 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.
Highlights
The three dimensional (3D) structures of chromosome vary with the developmental stage [1] and cell types, which implies that knowledge of chromosome structure and dynamics is key to understanding their link to gene regulation [2]
Structure and dynamics of interphase chromatin in space and time hold the key to understanding the cell type-dependent gene regulation
To study dynamics of chromosomes we modified the original Minimal Chromatin Model (MiChroM), which is partially self-avoiding with an energetic penalty for each crossing, by imposing a strict self-avoidance constraint and performed Brownian dynamics simulations. Discussing their dynamic properties using various correlation functions, we show that the Spatiotemporal dynamics of chromatin loci basic features of the chromatin dynamics reported in the recent experiments [44, 45] can be explained quantitatively by the crumpled, hierarchical, territorial, summarized as space-filling organization of chromatin chain
Summary
The three dimensional (3D) structures of chromosome vary with the developmental stage [1] and cell types, which implies that knowledge of chromosome structure and dynamics is key to understanding their link to gene regulation [2]. A well-designed chromosome structure can facilitate long range transcriptional regulation by keeping two distal genomic loci of enhancer and promoter in proximity [3,4,5]. Hierarchical organization of chromosomes are inferred from the patterns of Hi-C maps which measure mean contact frequencies of cross-linking between DNA segments based on an ensemble of millions of fixed cells. Hi-C data at submegabase resolution offer glimpses into the structure of TADs (topologically associated domains), the functional building blocks of interphase chromosome [7, 8]. Genome-wide Hi-C maps at even higher resolution of Oð10Þ Kb suggests that each type of compartment is associated with distinct epigenetic pattern, further segregating into six sub-compartments [9]. Fluorescence images visualizing real-time chromatin dynamics in vivo [10,11,12,13] allow us to decipher the link between structure, dynamics, and function [14,15,16]
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