The “Self-Stirred” Genome: Dynamics, Flows and Rheology

Abstract

Chromatin structure and dynamics control all aspects of DNA biology yet are poorly understood. In interphase, time between two cell divisions, chromatin fills the cell nucleus in its minimally condensed polymeric state. Chromatin serves as substrate to a number of biological processes, e.g. gene expression and DNA replication, which require it to become locally restructured. These are energy-consuming processes giving rise to non-equilibrium dynamics. Chromatin dynamics has been traditionally studied by imaging of fluorescently labeled nuclear proteins and single DNA-sites, thus focusing only on a small number of tracer particles. Recently, we developed an approach, displacement correlation spectroscopy (DCS) based on time-resolved image correlation analysis, to map chromatin dynamics simultaneously across the whole nucleus in cultured human cells [1]. DCS revealed that chromatin movement was coherent across large regions (4-5μm) for several seconds. Regions of coherent motion extended beyond the boundaries of single-chromosome territories, suggesting elastic coupling of motion over length scales much larger than those of genes [1]. These large-scale, coupled motions were ATP-dependent and unidirectional for several seconds. Following these observations, we developed a hydrodynamic theory [2] and a microscopic model [3] of active chromatin dynamics. In addition, we developed a novel strategy of using naturally present cellular probes to study genome rheology [4,5]. In this work we continue in our efforts to elucidate the mechanism and function of the chromatin dynamics in interphase. [1] Zidovska A, Weitz DA, Mitchison TJ, PNAS, 2013 [2] Bruinsma R, Grosberg AY, Rabin Y, Zidovska A, Biophys J, 2014 [3] Saintillan D, Shelley MJ, Zidovska A, PNAS 2018 [4] Caragine CM, Haley SC, Zidovska A, PRL, 2018 [5] Caragine CM, Haley SC, Zidovska A, eLife, 2019