(735e) A New Coarse-Grained Model of Chromosome Organization

The organization of chromosomes within eukaryotic cells plays a critical role in all genetic processes, including transcription, replication, repair, and recombination. There currently exist two main categories of polymer models aimed at capturing the features of chromosome organization. The first class of models accounts for long-range interactions between distant parts of the chromosome through formation of different kinds of loops. Fluorescent microscopy distance measurements strongly indicate existence of loops and are in agreement with predictions from such a model. The second class of models relies on the fractal folding nature of the chromosome to account for the structure and long-range interactions in chromosomes. This model reproduces the experimentally obtained genome wide contact probability measurements.

We present here a new coarse-grained lattice animal model of chromosomal organization that represents chromosome loops at different length scales, leading to a self-similar fractal structure. This representation is aimed at reconciling the differences between the two existing models of chromosome organization based on contact probability and distance measurements respectively. Monte-Carlo simulations for the reorganization of the lattice animal were carried out with varying interactions and confinement potentials. The simulations indicate that the probability of loops of size s decays as a power law, P(s) ~ s ^-α, where the value of α lies between 2.0 and 1.1. The simulation results for the decay of probability for polymers with excluded volume and bending potentials are found to be in agreement with existing genome wide contact probability measurements. Additionally, the simulations indicate that the scaling exponent ν connecting the radius of gyration Rg with the number of segments N lies between 0.25 and 0.5, in good agreement with variations in distance measurements of chromosome domains within cell nuclei.