Partial Unwrapping and Histone Tail Dynamics in Nucleosome Revealed by Coarse-Grained Molecular Simulations

Nucleosomes, basic units of chromatin, are known to show spontaneous DNA unwrapping dynamics that are crucial for transcriptional activation, but its structural details are yet to be elucidated. Here, employing a coarse-grained molecular model that captures residue-level structural details up to histone tails, we simulated equilibrium fluctuations and forced unwrapping of single nucleosomes at various conditions. The equilibrium simulations showed spontaneous unwrapping from outer DNA and subsequent rewrapping dynamics, which are in good agreement with experiments. We found several distinct partially unwrapped states of nucleosomes, as well as reversible transitions among these states. At a low salt concentration, histone tails tend to sit in the concave cleft between the histone octamer and DNA, tightening the nucleosome. At a higher salt concentration, the tails tend to bound to the outer side of DNA or be expanded outwards, which led to higher degree of unwrapping. Of the four types of histone tails, H3 and H2B tail dynamics are markedly correlated with partial unwrapping of DNA, and, moreover, their contributions were distinct. Acetylation in histone tails was simply mimicked by changing their charges, which enhanced the unwrapping, especially markedly for H3 and H2B tails.