Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

28 - POS Board 28 DISCERNING THE EFFECTS OF LINKER HISTONES ON SINGLE AND POLY- NUCLEOSOMAL ARRAYS WITH ALL-ATOM SIMULATIONS Jeff Wereszczynski 1 ; 1 Illinois Institute of Technology, Physics & The Center for Molecular Study of Condensed Soft Matter, Chicago, Illinois, United States Linker histones are essential epigenetic regulators which exert their influence by binding to and stabilizing the nucleosome core particle. Experiments have demonstrated that his can have dramatic effects on both the local and large-scale structures of chromatin fibers. Although they have been extensively studied, the principles underlying the molecular mechanisms of these proteins remain poorly understood. Here, I will discuss a series of all-atom molecular dynamics simulations aimed at discerning the effects of linker histone binding on both single nucleosomes and poly-nucleosomal arrays. Results of single nucleosome simulations show that on-dyad binding is energetically favored, whereas off-dyad binding is likely entropically favored irrespective of the linker histone isoform studied. Binding in each of these locations has distinct effects on the structure and dynamics of linker DNA. Simulations of octa-nucleosomal arrays show that these effects propagate into large scale changes in the structure and dynamics of chromatin. In these models of compact chromatin fibers, it is shown that H1 binding creates tighter and stiffer structures that better maintain tetra-nucleosomal repeats than similar systems that lack linker histones. Together, these results highlight the roles of linker histones in maintaining compact chromatin fibers and help reveal the physical processes underlying their mechanisms.

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