Tension-dependent Free Energies of Nucleosome Unwrapping

TL;DR

This study uses a coarse-grained model to quantify the tension-dependent free energies involved in nucleosome unwrapping, highlighting the roles of electrostatic interactions, histone modifications, and DNA sequence in nucleosome stability.

Contribution

It introduces a detailed simulation approach that accurately reproduces unwrapping forces and elucidates factors affecting nucleosome stability and regulation.

Findings

Model reproduces unwrapping forces quantitatively

Electrostatic interactions significantly influence unwrapping

Histone tails stabilize nucleosomal DNA outer turn

Abstract

Nucleosomes form the basic unit of compaction within eukaryotic genomes and their locations represent an important, yet poorly understood, mechanism of genetic regulation. Quantifying the strength of interactions within the nucleosome is a central problem in biophysics and is critical to understanding how nucleosome positions influence gene expression. By comparing to single-molecule experiments, we demonstrate that a coarse-grained molecular model of the nucleosome can reproduce key aspects of nucleosome unwrapping. Using detailed simulations of DNA and histone proteins, we calculate the tension-dependent free energy surface corresponding to the unwrapping process. The model reproduces quantitatively the forces required to unwrap the nucleosome, and reveals the role played by electrostatic interactions during this process. We then demonstrate that histone modifications and DNA sequence can have significant effects on the energies of nucleosome formation. Most notably, we show that histone tails are crucial for stabilizing the outer turn of nucleosomal DNA.