(484d) The Role of DNA Sequence in Nucleosome Positioning and Sliding

Nucleosomes provide the basic unit of compaction in eukaryotic genomes and the mechanisms that dictate their position along a DNA sequence are of central importance to epigenetics. In this work, we use molecular models of DNA and proteins to explore the sequence dependent cues that dictate nucleosome positioning. Using high-resolution coarse-grained simulations and free energy calculation techniques, we examine the mechanism by which DNA sequences reposition to find their binding site around the histone protein core. We show that this mechanism is strongly dependent on DNA sequence and that DNA slides around the histone by either a screw-like or loop-like mechanism. These results explain how sequence, manifested as the shape of the DNA molecule, dominates molecular recognition in the problem of nucleosome positioning.