DNA Sequence and Histone Core Composition Control the Unwrapping of DNA from Nucleosome Core Particles

Abstract

As controlling access to DNA is a major component of transcriptional regulation, understanding the effects of interactions between core proteins and the DNA is crucial to gaining an overall understanding of transcription. We report on the use of small angle X-ray scattering with contrast variation (CV-SAXS) to analyze DNA unwrapping from nucleosome core particles. Interactions between the histone core and the DNA are destabilized using increasing concentrations of neutral salt, lowering the strength of electrostatic interactions that bind the components together. As the complex is destabilized many unwrapping states are accessible and the DNA explores possible unwrapping pathways. The CV-SAXS data reports on full range of structures present in the sample. They are fit using sequence-dependent models of unwrapped structures with thermal motions, selected by an ensemble optimization method [1]. Different combinations of DNA sequence and histone composition also alter their interactions, and the unwrapped structures reflect biophysical differences in the nucleosome compositions. 1. Mauney A., Tokuda J.M., Gloss L.M., Gonzalez O., Pollack L. Local DNA sequence controls the cooperativity and asymmetry of DNA unwrapping from nucleosome core particles. Biophys J. 2018 Sep 4;115(5):773-781