From Macroscopic to Mesoscopic Models of Chromatin Folding

An overview of the evolution of macroscale to mesoscale computer models for simulation of chromatin, the protein nucleic acid fiber that stores the DNA in higher organisms, is presented. Many biological questions concerning fiber structure remain a puzzle. The sheer size and range of spatial and temporal scales require tailored multiscale models. Our first-generation macroscopic models ignored histone tail flexibility but generated insights info preferred zigzag configurations and folding/unfolding dynamics. The second-generation mesoscale models incorporate histone tail flexibility, linker histones, and divalent ion effects to reveal the profound compaction induced by linker histones and the polymorphic fiber architecture at divalent salt environments, with a small fraction of the linker DNAs bent rather than straight for optimal compaction. Our chromatin model can be extended further to study many important biological questions concerning posttranslational modifications, fiber dimension variations as a function of linker DNA length variations, and higher-order fiber topologies.