Centromere Tethering Confines Chromosome Domains

• Chromatin tethering at the centromere and telomere affects confinement and stiffness
• Cohesin depletion results in reduced confinement and effective spring constant
• Nucleosome depletion leads to increased confinement and effective spring constant
• Tethering and confinement underlie chromosome territory formation and fluctuation

SummaryThe organization of chromosomes into territories plays an important role in a wide range of cellular processes, including gene expression, transcription, and DNA repair. Current understanding has largely excluded the spatiotemporal dynamic fluctuations of the chromatin polymer. We combine in vivo chromatin motion analysis with mathematical modeling to elucidate the physical properties that underlie the formation and fluctuations of territories. Chromosome motion varies in predicted ways along the length of the chromosome, dependent on tethering at the centromere. Detachment of a tether upon inactivation of the centromere results in increased spatial mobility. A confined bead-spring chain tethered at both ends provides a mechanism to generate observed variations in local mobility as a function of distance from the tether. These predictions are realized in experimentally determined higher effective spring constants closer to the centromere. The dynamic fluctuations and territorial organization of chromosomes are, in part, dictated by tethering at the centromere.