Nuclear Architecture Controls the Timescales of Genomic Interactions

Many processes in biology, from antibody production to tissue differentiation, require physical contact between distant genomic segments. The segments must find each other quickly despite chromatin packing and the crowded environment of the cell nucleus. What are the consequences of chromatin architecture for the timescales of genomic interactions? To address this question we analyzed 3D genomic trajectories from a novel multi-color imaging approach applied to live pro-B cells. We find that anomalous diffusion in a viscoelastic environment is the dominant mechanism of chromatin motion. We combined molecular dynamics simulations with statistical and polymer physics to reveal some of the principles by which nuclear architecture controls genomic timescales. Specifically, we built a hierarchy of polymer physics models reflecting a spectrum of chromatin configurations, such as loops and loop domains. We established quantitative relationships between spatial and genomic distances of two segments, and between their encounter time and spatial separation. These models provide quantitative, physical interpretations of the observed genomic motion and generate testable predictions regarding the structure-dynamics relationship at different levels of genome organization.