Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Monday Speaker Abstracts

HISTONE TRAFFICKING DURING CHROMATIN REPLICATION Mair Churchill University of Colorado, Denver, USA No Abstract

CHROMATIN DYNAMICS STUDIED BY THE GAUSSIAN NETWORK MODEL: SHORT- AND LONG-RANGE COUPLINGS BETWEEN GENE LOCI Ivet Bahar 1 ; She Zhang 1 ; 1 University of Pittsburgh, Computational and Systems Biology, Pittsburgh, Pennsylvania, United States Understanding the three-dimensional (3D) architecture of chromatin and its relation to gene expression and regulation is fundamental to understanding how the genome functions. Advances in Hi-C technology now permit us to study 3D genome organization, but we still lack an understanding of the structural dynamics of chromosomes. The dynamic couplings between regions separated by large genomic distances (> 50 megabases) have yet to be characterized. We recently adapted a well-established protein-modeling framework, the Gaussian Network Model (GNM), to model chromatin dynamics using Hi-C data (1). We show that the GNM can identify spatial couplings at multiple scales: it can quantify the correlated fluctuations in the positions of gene loci, find large genomic compartments and smaller topologically-associating domains (TADs) that undergo en-bloc movements, and identify dynamically coupled distal regions along the chromosomes. We show that the predictions of the GNM correlate well with genome- wide experimental measurements. We use the GNM to identify novel cross-correlated distal domains (CCDDs) representing pairs of regions distinguished by their long-range dynamic coupling and show that CCDDs are associated with increased gene co-expression. We then analyze the GNM results obtained from the Hi-C maps of different cell types to show that while GNM mode shapes are mainly conserved, the contributions of individual modes to the overall dynamics of cell genome are cell-type specific. Combined with the previous findings on the association between chromosomal mobility and accessibility, computational results suggest that the spectrum of GNM modes in the low frequency regime are common modules of chromosomal dynamics shared by different cell types. How they are assembled may give rise to diverse gene expressions and finally lead to differentiated cellular phenotypes. Reference: Sauerwald N, Zhang S, Kingsford C, Bahar I. (2017) Chromosomal dynamics predicted by an elastic network model explains genome-wide accessibility and long-range couplings Nucleic Acids Res 45 :3663-3673

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