(63d) Effects of DNA Methylation On DNA-Histone Interactions and Nucleosome Positions

DNA occurs in CpG dinucleotides when a methyl group is added at the carbon 5 position of the C base ring, and it has an important role in regulating gene expression in higher eukaryotes. It is known that when cytosine bases are methylated, gene is silenced, but the precise role of methylated DNA in this process is still debated, and the mechanism by which methylation affects gene expression remains poorly understood. One way in which DNA methylation could regulate expression is by modifying the positions of nucleosomes, which in turn can regulate gene transcription by blocking the access of transcription factors to the gene. Here, we test this hypothesis by performing MD simulations of short DNA segments in solution and in the nucleosome, using an all atom force field. DNA conformations are characterized using the six rigid body base-pair step parameters, minor groove width, hybridization state and phosphate solvent exposure, and the changes in free-energy of the nucleosome are calculated upon cytosine methylation.