Physical Modeling of Stress Communication between Chromosome Loci

2016 
The organizational dynamics of chromosomal DNA are critical to many biological processes including genetic regulation, recombination, condensation, and segregation. The physical understanding of such processes would be greatly improved by predictive, quantitative modeling that can be directly compared to experimental measurements. Previous work has examined or modeled either single locus dynamics or the organization of multiple loci through static or ensemble measurements. New tools in fluorescence microscopy now enable the real-time tracking of several loci simultaneously, requiring additional physical model development to interpret the observed behaviors. Toward this end, we employ a polymer dynamics framework to predict the correlation in the velocities of two loci connected by chromatin. This predictive theory uses a minimal number of fitting parameters and reveals that the signature of correlated motion between loci can be identified by varying the lag time between locus position measurements. Our results predict that as the lag time interval increases, the dual-loci dynamic behavior changes from being uncorrelated to behaving as an effective single locus. This transition is determined by the timescale of the stress communication between loci through the intervening segments. We show that this single transition timescale is the only fit parameter needed to make direct quantitative comparisons to the in vivo motion of fluorescently labeled chromosome loci. We further show that our predictions are qualitatively consistent with recently published experimental measurements of the motion of sets of two loci on a single chromosome in budding yeast during interphase. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion.
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