Understanding the three-dimentional structures of chromatins at nucleosome resolution.

Abstract

In human cells, the genomic DNA are associated with proteins to form compact chromatin structures in the nucleus. In the past decades, significant efforts have been made to obtain the three-dimensional (3D) structures of chromatin and to understand the mechanism driving the folding process of the genome, with the goal of understanding the relationship between the 3D structures and the gene regulation and expression. Recently, the advance of experimental techniques makes it possible to investigate the structural features in chromatin, such as compartmentalization and loops, at fine resolutions, which also inspired us to develop a physical model for understanding the folding mechanism of chromatin structures at comparable resolutions. Here, we introduce a theoretical model at nucleosome resolution which not only generates chromatin conformations consistent with experimental data, but also facilitates the investigation the folding mechanisms, such as loop formation as well as potential underlying regulations between different loops. In this model, every nucleosome in the chromatin is represented by a bead with the same diameter of the nucleosome while neighboring beads are connected at the distance comparable to the length of linker DNA between nucleosomes, which makes it possible to precisely compare the simulated chromatin conformations with experimentally measurable quantities. As an example, we calculate the chromatin volume concentrations from the simulated conformations, which are comparable to the experimental measures using ChromEMT. This model provides significant insights to chromatin 3D structures at fine resolutions, which also serves as a powerful tool for future investigations such as how structures affect gene regulations and expressions.