(89h) Unraveling Structural Motifs of Heterogeneous Chromatin through Coarse-Grained Modeling

Chromatin is a unique biopolymer consisting of repeats of nucleosomes connected by flanking segments of short linker-DNA. In previous work, we developed a bottom-up Brownian dynamics modeling approach to unveil the mesoscopic structure of chromatin. Through this model, we are able to identify the delicate interplay between DNA flexibility and the anisotropic inter-nucleosome interactions, and how each plays a role on the structure of chromatin. In the ideal case (homogeneous linker-length), chromatin is comprised of ordered trinucleosome motifs. However, in the cell nucleus nucleosomes diffuse along the DNA, generating heterogeneous fibers. Here, we assess chromatin structure subject to nucleosome dynamics through structural and thermodynamic analysis. We first demonstrate that the structure of heterogeneous fibers of various linker-DNA distributions is disordered, yet occupies the same volume. We then utilize free energy methods to determine the relative thermodynamic stability between homogeneous and heterogeneous chromatin.