Multi-scale simulations characterize the influence of H4K16 modifications on nucleosome dynamics

Post-translational modifications (PTM) on histones play a critical role in regulating gene expression and are closely correlated with disease. One kind of PTM, H4K16 acetylation, has been shown to weaken inter-nucleosomal interactions and make chromatin more accessible. Specifically, H4K16 acetylation has been demonstrated to weaken the interaction between residue lysine in H4 and the acidic patch in H2A by charge neutralization. Recently, propionylation (Pr) and butyrylation (Bu) of the same residue have been shown to couple metabolism with chromatin restructuring, but the mechanisms still remain unknown. In this work, we combine our coarse-grained DNA model and chromatin model in silico to elucidate the effect of PTM on dynamics of a 12 nucleosome array. To match the predictions from coarse-grained DNA and protein model, we re-parametrize the inter-nucleosome interactions of our chromatin model. Then replica exchange simulations are run to provide efficient sampling on dynamics of the 12 nucleosome array. We also provide avenues for future validation of our results by predicting experimental FRET efficiency distributions. Moreover, our analysis on chromatin accessibility and tetra-nucleosome motifs paves the way to further understanding of PTMs’ effects on chromatin dynamics.