ABSTRACT: Chromatin structure, dynamics, and function are being intensely investigated by a variety of methods, including microscopy, X-ray diffraction, nuclear magnetic resonance, biochemical crosslinking, chromosome conformation capture, and computation. A range of experimental techniques combined with modeling is clearly valuable to help interpret experimental data and, importantly, generate configurations and mechanisms related to the 3D organization and function of the genome. Contact maps, in particular, as obtained by a variety of chromosome conformation capture methods, are of increasing interest due to their implications on genome structure and regulation on many levels. In this perspective, using seven examples from our group's studies, we illustrate how molecular modeling can help interpret such experimental data. Specifically, we show how computed contact maps related to experimental systems can be used to explain structures of nucleosomes, chromatin higher-order folding, domain segregation mechanisms, gene organization, and the effect on chromatin structure of external and internal fiber parameters, such as nucleosome positioning, presence of nucleosome free regions, histone posttranslational modifications, and linker histone binding. We argue that such computations on multiple spatial and temporal scales will be increasingly important for the integration of genomic, epigenomic, and biophysical data on chromatin structure and related cellular processes.
