Integrative modeling of the genome structure and dynamics in fission yeast

• 成果类型: Article
• 署名作者: Shinkai, Soya; Namba, Toshinori; Sugawara, Takeshi; Hagiwara, Soya; Onami, Shuichi; Haraguchi, Tokuko; Hiraoka, Yasushi; Awazu, Akinori; Ueno, Masaru; Tate, Shin-ichi
• 署名单位: RIKEN; Hiroshima University; University of Osaka; Hiroshima University; Hiroshima University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2612002123
• 发表日期: 2026-09-15
• 页码: e2612002123
• 关键词: chromatin dynamics; 3d genome; polymer modeling; fission yeast; meiotic prophase; ORGANIZATION; MOVEMENT; mobility; reveals; microtubules; architecture; centromeres; principles; complex

摘要

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. By integrating these dynamics with contact data through polymer modeling of Hi-C data, we build a physics-based digital twin of the S. pombe genome consistent with the spatiotemporal dynamics of interphase chromatin. We validate it against 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 similar to 150 s, whereas the remaining loci relax within similar to 70 s. We measure semiperiodic dynamics of SPB motion, including a characteristic 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 modeling 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.