Chromatin Folding Via Coarse-Grained Multi-Scale Simulation

The compaction of eukaryotic DNA in to chromatin represents an essential, yet poorly understood mechanism for controlling gene expression. Errors during compaction are associated with numerous diseases, and therefore elucidating the molecular factors that control compaction is a central goal of genetics. A significant challenge in studying chromatin compaction is the many length scales involved, typically ranging from angstroms to microns. In this work, we present a multi-scale approach that couples a detailed molecular model of the nucleosome to a coarse-grained mesoscale model of chromatin. We show that this approach can reproduce the dynamics and thermodynamics of available experimental measurements, and is computationally efficient enough to examine the self-assembly of large regions of chromatin. Notably, we show that subtle features of the chromatin fiber, such as the underlying DNA sequence, can have a significant impact on the stability and accessibility of different chromatin structures. The work presented here represents important steps toward understanding the molecular processes that dictate the dynamics and structure of chromatin.