Integrative modelling of the genome structure and dynamics in fission yeast

Genome organization in the nucleus is highly structured and dynamic. Recent advances in genomic technology have enabled the measurement of genome-wide architecture and locus-specific motion, yielding contact maps and live-cell trajectories. However, these outcomes are derived from different modalities and are not directly comparable, with their quantitative integration being a key challenge. Here we establish a genome-wide live-cell imaging platform in fission yeast Schizosaccharomyces pombe, tracking 131 chromosomal loci, along with the spindle pole body (SPB) and nucleolus, to construct a quantitative map of locus dynamics. We integrate these dynamics with contact data through physics-based polymer modelling of Hi-C data. The resulting model reproduces genome-wide mobility patterns and known architectural features, including centromere and telomere clustering. The model also identifies distinct dynamical regimes: centromere- and telomere-proximal loci relax within ~150 s, whereas the remaining loci relax within ~70 s. SPB motion exhibits an oscillatory peak near 225 s and 1/f fluctuations. We use the model with SPB-directed forcing to show how these low-frequency components propagate through the genome to drive genome-wide chromatin displacements. Together, this predictive physics-based framework integrates genome structure and dynamics to reveal how nuclear mechanical driving forces shape chromosome motion, linking mechanically-driven chromatin responses to genome maintenance and regulation.