Exploring the Free Energy Landscape of Nucleosomes
Bin Zhang, Weihua Zheng, Garegin A. Papoian, and Peter G Wolynes
J. Am. Chem. Soc., Just Accepted Manuscript
Publication Date (Web): June 14, 2016
Copyright © 2016 American Chemical Society
Rice University scientists simulated a nucleosome coiled in DNA to discover the interactions that control its unwinding. The DNA double helix binds tightly to proteins (in red, blue, orange and green) that make up the histone core, which exerts control over the exposure (center and right) of genes for binding. Credit: Wolynes Lab/Rice University
The nucleosome is the fundamental unit for packaging the genome. A detailed molecular picture for its conformational dynamics is crucial for understanding transcription and gene regulation. We investigate the disassembly of single nucleosomes using a predictive coarse grained protein DNA model with transferable force fields. This model quantitatively describes the thermodynamic stability of both the histone core complex and the nucleosome, and predicts rates of transient nucleosome opening that match experimental measurements. Quantitative characterization of the free energy landscapes reveals the mechanism of nucleosome unfolding in which DNA unwinding and histone protein disassembly are coupled. The interfaces between H2A-H2B dimers and the (H3-H4)2 tetramer are first lost when the nucleosome opens releasing a large fraction but not all of its bound DNA. For the short strands studied in single molecule experiments, the DNA unwinds asymmetrically from the histone proteins, with only one of its two ends preferentially exposed. The detailed molecular mechanism revealed in this work provides a structural basis for interpreting experimental studies of nucleosome unfolding.
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