Description:

Many processes in biology, from antibody production to tissue differentiation, require physical interactions between distant DNA segments. Genomic interactions are, however, complicated by multi-level chromosome organization, macromolecular crowding, and active processes in the cell nucleus. How do DNA segments move and interact within such a complex nuclear environment? What are the consequences of chromosome organization for the dynamics of DNA segments and for the timescales of genomic encounters? To address these questions, we analyzed 3D trajectories of fluorescently labeled gene segments from novel imaging measurements on live immune cells, and found that the motion of DNA segments is strongly subdiffusive. We proposed that this strongly subdiffusive motion is caused by the viscoelastic nature of chromatin – the DNA-protein complex – in the nucleus, and that the subdiffusion can be modeled by fractional Langevin dynamics. To further explore the microscopic origin of the viscoelasticity, we modeled chromatin with coarse-grained molecular dynamics simulations. We identified crosslinks between chromatin as key to its observed viscoelasticity. Our findings suggest that the formation of chromosomal domains may be accompanied by a transition from a liquid-like state to a gel-like state. Finally, through combined fractional Langevin modeling and molecular dynamics simulations, we showed that the encounter times for remote gene segments are largely controlled by the spatial size and physical state of chromosomal domains.

Dr. Yaojun Zhang, Center for the Physics of Biological Function, Princeton University

Keywords: Physics, Astronomy, Complex Systems