Sevastianos Korsak
supervisor: Dariusz Plewczynski
The structure of chromatin can be seen as the superposition of two main factors: compartmentalization, which organizes the genome in A and B compartments and loop extrusion, which is responsible for the formation of topologically associated domains (TADs). The loop extrusion process is carried by Smc complexes with ring-like structure such as cohesin or condensin, which are responsible for the formation of loops, whereas CTCF proteins or nuclesomes work as barriers for the motion of cohesin and they are capable of constructing stripes in the boundaries of TADs. Here we present a way to simulate chromosomal regions with more than one TAD as a stochastic Monte Carlo simulation process. In this method, we locate CTCF proteins according to the peaks of CTCF ChIP-seq data and we define a relocation probability with which each cohesin can randomly relocate to another place of the chromatin fibre. The folding of chromatin plays the role of the ergodic mean of the simulation, which help us to understand when it has converged to the equilibrium state. Having reached the equilibrium we can produce 3d structures by a molecular simulation model called "Spring model" and we end up with a thermodynamical ensemble whose average distance heatmap is similar to the CTCF ChIA-PET data. Finally, we succeeded to predict the burning period of the simulation and the final state of the Markovian process from the input parameters by using a simple system of nonlinear differential equations.