The nucleosome consists of a short stretch of DNA wrapped around a protein cylinder, and is the fundamental unit of chromatin, which compacts the DNA into the cell nucleus. The nucleosome is known...Show moreThe nucleosome consists of a short stretch of DNA wrapped around a protein cylinder, and is the fundamental unit of chromatin, which compacts the DNA into the cell nucleus. The nucleosome is known to transiently partially unwrap or 'breathe' \textit{in vitro}, exposing DNA which would otherwise be sterically inaccessible to enzymes. Breathing is investigated for its potential importance \textit{in vivo} in both essential DNA processes, and in higher-order chromatin organisation. In this thesis we present a two-parameter physical statistical model of the breathing process based on steric enzyme accessibility, the energetics of the bent DNA molecule, and the adsorption of the DNA upon the proteins. We estimate the elastic energy using Monte Carlo simulations of a coarse-grained model of the nucleosomal DNA, and we fit the model to the available experimental results. We find in agreement with experimental studies that site accessibility decays exponentially toward the centre sites, and that highly asymmetric breathing behaviour is possible due to the very sensitive dependence of breathing upon energy distribution, and in turn, sequence.Show less
