468232 Tension-Dependent Free Energies of Nucleosome Unwrapping

Thursday, November 17, 2016: 10:30 AM
Yosemite C (Hilton San Francisco Union Square)
Joshua Lequieu, Andres Cordoba and Juan J. de Pablo, Institute for Molecular Engineering, University of Chicago, Chicago, IL

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.

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See more of this Session: Thermodynamics of Biomolecular Folding and Assembly
See more of this Group/Topical: Engineering Sciences and Fundamentals