Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Wednesday Speaker Abstracts

UNVEILING CHROMATIN FIBER CONDENSATION THROUGH MANY-BODY NUCLEOSOME INTERACTIONS Joshua Moller 1 ; Joshua Lequieu 1 ; Juan J de Pablo 1,2 ; 1 University of Chicago, Institute for Molecular Engineering, Chicago, Illinois, United States 2 Argonne National Laboratory, Lemont, Illinois, United States The physics governing nucleosome interactions influence structural features of chromatin across a wide range of length-scales. Here, we assess the extent of these interactions through Brownian dynamics simulations using our recently-developed coarse-grained model of chromatin. This new model represents nucleosomes as rigid bodies to efficiently study the underlying nucleosome physics within the chromatin fiber. To this extent, simulations are used to interpret the hierarchy of interactions in chromatin fibers by quantifying the energetics of small- fibers, including di- and trinucleosomes, and isolating the factors that facilitate condensed configurations. Among these factors, we consider the influences of DNA sequence, nucleosome repeat length, and inclusion of the H1 linker histone. These small-fiber results are then used to assess the structure of larger chromatin fibers, revealing that the configurations of nucleosomes in larger fibers favor are influenced by those exhibited in the small-scale systems. We further demonstrate that correlations exist in the chromatin fiber beyond three body interactions. Lastly, we show that the linker histone significantly shifts the energetic minima of the smaller systems, which corresponds to similar configuration changes of larger chromatin fiber structure.

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