Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

17-POS Board 17 MULTI-SCALE ANALYSIS OF CHROMOSOME STRUCTURE AND DYNAMICS: FROM 3D TO 4D Anna Lappala 1 ; Karissa Y Sanbonmatsu 1 ; 1 Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, United States We use fractal dimension analysis to study the morphology and the dynamics of chromatin folding. The fractal dimension provides a method for quantifying properties such as lacunarity (voids in a 3D structure) and asphericity, resulting in a unique measure of local connectivity and compaction morphology. The evolution of the fractal dimension as a function of compaction relates chromatin density and morphology to the process of folding. Using Molecular Dynamics simulations of coarse-grained polymers, we demonstrate a linear relation between the number of contacts (i.e., local density) z and packing fraction f, showing that a system becomes dynamically arrested, behaving like an amorphous solid (i.e. glass) at f~0.58. It has been demonstrated that similarly to glasses, density and local diffusivity in chromatin are non-uniform and dynamics heterogenous, with locally confined- and structurally open domains that are critical for its biological function. To demonstrate the connection between specific chromosome interactions and compaction, we compare the dynamics of chromatin with regular nucleosomes to macroH2A variants. We use experimental HiC maps to infer a 3D structure and calculate fractal dimensions for structures of increasing complexity from well-characterized nucleosome arrays to more complex 30-nm folds and even extend our approach to complete chromosomes. We analyze the evolution of fractal dimension over time, characterizing the dynamics of chromatin folding and distinguishing compact (inactive), extended (active) and intermediate (epigenetically poised) architectures.

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