Unwinding and rewinding the nucleosome inner turn: Force dependence of the kinetic rate constants

TL;DR

This paper presents a quantitative model for the force-dependent unwinding and rewinding rates of nucleosome inner turns, integrating elastic energy barriers and histone-DNA interactions, and compares it with recent experimental data.

Contribution

A novel coarse-grained model combining elastic free energy and specific bonds accurately describes nucleosome dynamics under force, aligning well with experimental results.

Findings

Model fits experimental data well at lower forces.

Elastic barriers and histone-DNA contacts are crucial for nucleosome stability.

High-force disassembly may involve alternative pathways.

Abstract

A simple model for the force-dependent unwinding and rewinding rates of the nucleosome inner turn is constructed and quantitatively compared to the results of recent measurements [A. H. Mack et al., J. Mol. Biol. 423, 687 (2012)]. First, a coarse-grained model for the histone-DNA free energy landscape that incorporates both an elastic free energy barrier and specific histone-DNA bonds is developed. Next, a theoretical expression for the rate of transitions across a piecewise linear free energy landscape with multiple minima and maxima is presented. Then, the model free energy landscape, approximated as a piecewise linear function, and the theoretical expression for the transition rates are combined to construct a model for the force-dependent unwinding and re-winding rates of the nucleosome inner turn. Least-mean-squares fitting of the model rates to the rates observed in recent experiments rates demonstrates that this model is able to well describe the force-dependent unwinding and rewinding rates of the nucleosome inner turn, observed in the recent experiments, except at the highest forces studied, where an additional ad hoc term is required to describe the data, which may be interpreted as an indication of an alternate high-force nucleosome disassembly pathway, that bypasses simple unwinding. The good agreement between the measurements and the model at lower forces demonstrates that both specific histone-DNA contacts and an elastic free energy barrier play essential roles for nucleosome winding and unwinding, and quantifies their relative contributions.