Free-energy landscape of mono- and dinucleosomes: Enhanced rotational flexibility of interconnected nucleosomes.

Abstract

The nucleosome represents the basic unit of eukaryotic genome organization, and its conformational fluctuations play a crucial role in various cellular processes. Here we provide insights into the flipping transition of a nucleosome by computing its free-energy landscape as a function of the linking number and nucleosome orientation using the density-of-states Monte Carlo approach. To investigate how the energy landscape is affected by the presence of neighboring nucleosomes in a chromatin fiber, we also compute the free-energy landscape for a dinucleosome array. We find that the mononucleosome is bistable between conformations with negatively and positively crossed linkers while the conformation with open linkers appears as a transition state. The dinucleosome exhibits a markedly different energy landscape in which the conformation with open linkers populates not only the transition state but also the global minimum. This enhanced stability of the open state is attributed to increased rotational flexibility of nucleosomes arising from their mechanical coupling with neighboring nucleosomes. Our results provide a possible mechanism by which chromatin may enhance the accessibility of its DNA and facilitate the propagation and mitigation of DNA torsional stresses.