The intriguing dynamics of chromatin folding and assembly

ABSTRACT We investigate the dynamics of chromatin folding based on the “strings and binders” (SBS) model with molecular dynamics simulation. SBS model is a coarse-grained model considering a self-avoiding chain interacting with diffusive binders. By introducing transition among different categories of beads with specific transition cycles and transition probabilities, our model is capable of introducing different dynamics quantitatively during the folding process, thus capturing variety of phenomena related to chromatin dynamics. Firstly, roles of dynamics in the process of chromatin folding were examined. We discovered that there is a minimum gyration of chromatin under varying characteristic times of transition which indicates neither dramatically dynamic nor static folding process is optimal for chromatin to reach stable states with relatively low free energy. Secondly, it is noticeable that when beads transit from or into others in distinct dynamics, the equilibrium concentrations are distinct as well. As a consequence, the distribution of chromatin loop length is relevant to the dynamics of binders which can be modified by complex such as Wings apart-like protein homolog (Wapl) and SCC2/SCC4 cohesin loader complex (SCC2/SCC4). Finally, our model is able to reproduce contact matrices of both wild type HAP1 cell and ΔWAPL HAP1 cell obtained from Hi-C technology with a relatively high accuracy. Our model recapitulate the accumulating contacts at the corners of TADs and vanishing short-range contacts along the diagonal, manifesting the difference of chromatin structures before and after eliminating WAPL. STATEMENT OF SIGNIFICANCE Our model includes reciprocal transition among beads in SBS model to introduce different dynamics in chromatin folding process. Our model is able to examine the roles of dynamics in chromatin folding, reveal the loop length variation due to the concentration imbalance caused by distinct dynamics and reproduce contact matrices of both wild type and WAPL-deficient cells. Our research work provides a model to investigate the dynamics of chromatin folding quantitatively and displays its significance of revealing multiple experimental results using computational tools.