Effect of nucleosome density, nucleosome positions and cohesin on the structure of chromatin studied with Monte Carlo simulations

The structure of chromatin is important for the regulation of transcriptional activity in the nucleus. It is influenced by several factors, such as nucleosome density, which varies over a wide range, the position of nucleosomes on DNA, which is actively regulated by the cell, and the binding of cohesin and CTCF by looping. We applied Monte Carlo computer simulations to study different systems up to 2 Mbp in size under different conditions, and compared the results with experimental data from conformation capture experiments, high-resolution microscopy, and electron microscopy. We identified cell-to-cell variability in the number of bound nucleosomes, linker histones, and internucleosomal interaction strength as a function of a region's transcriptional activity. Chromatin looping mediated by CTCF and cohesin increased the number of contacts between distant sites. These contacts were dependent on nucleosome positions. The structure of chromatin under density conditions, as observed in the nucleus modeled by periodic boundary conditions, is determined by the distribution of nucleosome positions. It controls accessibility by modulating the diffusion behavior of factors in the chromatin network.