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Abstract
Fingerprints of the three-dimensional organization of genomes have emerged using advances in Hi-C and imaging techniques. However, genome dynamics is poorly understood. Here, we create the chromosome copolymer model (CCM) by representing chromosomes as a copolymer with two epigenetic loci types corresponding to euchromatin and heterochromatin. Using novel clustering techniques, we establish quantitatively that the simulated contact maps and topologically associating domains (TADs) for chromosomes 5 and 10 and those inferred from Hi-C experiments are in good agreement. Chromatin exhibits glassy dynamics with coherent motion on micron scale. The broad distribution of the diffusion exponents of the individual loci, which quantitatively agrees with experiments, is suggestive of highly heterogeneous dynamics. This is reflected in the cell-to-cell variations in the contact maps. Chromosome organization is hierarchical, involving the formation of chromosome droplets (CDs) on genomic scale, coinciding with the TAD size, followed by coalescence of the CDs, reminiscent of Ostwald ripening.
Highlights
Fingerprints of the three-dimensional organization of genomes have emerged using advances in Hi-C and imaging techniques
Using simulations based on the resulting chromosome copolymer model (CCM), we show that chromosome dynamics is highly heterogeneous and exhibits many of the characteristics of out of equilibrium glassy dynamics, with coherent motion on μm scale, including stretched exponential decay of the scattering function (Fs(k,t)), a non-monotonicity behavior in the time dependence of the fourth order susceptivity associated with fluctuations in Fs(k, t)
The structures of the chromosome are arranged in such a way that segments with small genomic distance s are more likely to be in spatial proximity
Summary
Fingerprints of the three-dimensional organization of genomes have emerged using advances in Hi-C and imaging techniques. Some of the features in the contact maps, such as the probability P(s) that two loci separated by a certain genomic distance (s) are in contact, may be computed using a homopolymer model[4], without accounting for the epigenetic states, whereas fine structures such as TADs and compartments require copolymer or heteropolymer models[18,20,21,26]. Biological functions, such as the search for genes by transcription factors or mechanism for DNA damage repair, depend on genome structure and the associated dynamics. It is important to understand how the slow dynamics of the individual locus and long length scale coherent collective motions emerge from the highly organized chromosomes
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