Coarse-grained simulations of nucleosomes

Abstract

In eukaryotic cells, the nucleosome core particle (NCP) forms the basic unit of the genetic architecture. In NCPs, genomic DNA is tightly wound around an octameric core of histone proteins, much like thread wrapped around a spool. Recent experiments have shown that nucleosomes are highly dynamic, and often unwrap in an asymmetrical fashion at high ionic strengths, or in response to mechanical perturbations. By developing a sequence-specific coarse- grained model for DNA-protein complexes, which recapitulates various aspects of nucleosome structure and dynamics, we show how sequence-specificity of DNA-protein interactions is critical for nucleosome plasticity. Our force-field also captures the two-stage unwrapping observed in single-molecule pulling experiments. We further show that histone tails, which are hotspots for post-translational modifications, play a remarkable role in modulating the extent, as well as the direction of unwrapping. Our observations could set the stage for under...