Using deformation energy to analyze nucleosome positioning in genomes

Abstract

By modulating the accessibility of genomic regions to regulatory proteins, nucleosome positioning plays important roles in cellular processes. Although intensive efforts have been made, the rules for determining nucleosome positioning are far from satisfaction yet. In this study, we developed a biophysical model to predict nucleosomal sequences based on the deformation energy of DNA sequences, and validated it against the experimentally determined nucleosome positions in the Saccharomyces cerevisiae genome, achieving very high success rates. Furthermore, using the deformation energy model, we analyzed the distribution of nucleosomes around the following three types of DNA functional sites: (1) double strand break (DSB), (2) single nucleotide polymorphism (SNP), and (3) origin of replication (ORI). We have found from the analyzed energy spectra that a remarkable “trough” or “valley” occurs around each of these functional sites, implying a depletion of nucleosome density, fully in accordance with experimental observations. These findings indicate that the deformation energy may play a key role for accurately predicting nucleosome positions, and that it can also provide a quantitative physical approach for in-depth understanding the mechanism of nucleosome positioning.