Abstract
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.
Highlights
Nucleosomes, basic units of chromatin, are made of about 147 base pair double strand DNA wrapped 1.75 turns around a histone octamer [1]
We identified that 35 Å from the center of histone core corresponds to the boundary between the histone octamer core and the wrapped DNA, which makes concave surface
We investigated partial unwrapping dynamics of nucleosome by coarse-grained molecular dynamics simulations
Summary
Nucleosomes, folding units of chromatin, wrap DNA about 1.75 turns and provide bottlenecks for transcription. Recent experiments showed that nucleosomes are not rigid but dynamic, showing spontaneous and partial unwrapping which is important for transcriptional activation. One cannot directly watch DNA unwrapping at high resolution. Molecular dynamics simulations have high spatio-temporal resolution and can be powerful and complementary to experiments. We put forward coarse-grained modeling of protein-DNA interactions at residuelevel resolution, which is rather generic and can be applied to any protein-DNA complexes. By this method, we could reveal spontaneous and salt-concentration dependent. Partial unwrapping of DNA is correlated with certain parts of histone tail dynamics. Deleting positive charges in histone tails that mimics histone acetylation facilitated partial unwrapping, most significantly for H3 and H2B
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