Brownian Dynamics Simulation of Nucleosome Formation and Disruption under Stretching.pdf

Brownian Dynamics Simulation of Nucleosome Formation and Disruption under Stretching ∗ Wei Li, Shuo-Xing Dou, Peng-Ye Wang Laboratory of Soft Ma tter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100080, China Abstract Using a Brownian dynamics simulation, we numerically studied the interaction of DNA with histone and proposed an octamer-rotation model to describe the process of nucleosome formation. Nucleosome disruption under stretching was also simulated. The theoretical curves of extension versus time as well as of force versus extension are consistent with previous experimental results. Keywords: DNA, histone, interaction, nucleosome formation, nucleosome disruption 1. Introduction In all eukaryotic genomes, the basic unit of chromatin structure is nucleosome which is made up of 146 bp of DNA and histones — H2A, H2B, H3, H4 and H1 (H5) (Wolffe, 1998). Histones H2A, H2B, H3 and H4, with each contributing two molecules, form a histone octamer around which DNA wraps in approximate two turns in a left-handed way. H 1 (H5) is a linker histone. It binds at the point where DNA enters and exits the nucleosome. The histone octamer is a tripartite assembly in which a centrally located (H3-H4)2 tetramer is flanked by two H2A-H2B dimmers, and the eight histone molecules form a left-handed protein superhelix (Klug et al., 1980; Arents et al., 1991; Hamiche et al., 1996; Luger et al., 1997; Luger and Richmond, 1998). Nucleosome represents the first level of packing of DNA in chromatin in a nucleus. At a higher level, many nucleosomes form a ‘zig-zag’ structure (Woodcock et al., 1993; Leuba et al., 1994). As DNA is negatively charged and histones are positively charged, the main interaction between DNA and histones should be of electrostatic n