Uncovering the Relation between Inter-Nucleosome Energetics and Supramolecular Chromatin Structure

The supramolecular structure of chromatin is influenced by inter- and intra-nucleosome interactions. Central to these interactions, the flexible N-terminal domain histone tails have positively-charged sites that facilitate nucleosome interactions. Recent experiments have quantified inter-nucleosome interactions, but with differing results. With this work, we utilize coarse-grained brownian dynamics simulations with enhanced sampling techniques to provide insight into these experiments, and understand how the inter-nucleosome interactions influence chromatin structure. We quantify the anisotropic interaction energy and highlight the discrepancy between prior results through varying salt concentrations and counter-ion condensation effects. We then highlight that the interaction between the H4 tail and the H2A acidic patch introduces asymmetry into the interaction landscape, favoring a left-handed chromatin super-helix motif. To examine the effect of epigenetic modifications, we introduce acetylations to the H4 and H3 tails and assess the resulting energetic interactions. Lastly, we demonstrate how our results can be incorporated into a multi-scale model that can simulate large scale rearrangements of chromatin.