Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

25-POS Board 25 INTERPHASE HUMAN CHROMOSOME EXHIBITS OUT OF EQUILIBRIUM GLASSY DYNAMICS Guang Shi 1 ; Lei Liu 2 ; Changbong Hyeon 2 ; Devarajan Thirumalai 3 ; 1 University of Maryland at College Park, Institute of Physical Science and Technology, College Park, Maryland, United States 2 Korea Institute for Advanced Study, Seoul, Seoul, South Korea 3 University of Texas at Austin, Chemistry Department, Austin, Texas, United States 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.

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