3次元ゲノム構造とクロマチン動態をつなぐ高分子物理学

• Published in: 日本薬理学会年会要旨集 p. 3-B-S48-3
• Main Authors: 新海, 創也, 大浪, 修一
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: chromosome
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_3-B-S48-3

Chromatin fibers, as the substance of the genome, are biopolymers packed inside eukaryotic cells. The recent development of Hi-C has provided insights into the hierarchical organization of chromosomes as 3D genome structures. These structures include A/B compartments at the megabase scale, TADs spanning hundreds of kilobases, and smaller contact/loop domains. However, Hi-C technology relies on the chemical fixation of cells and chromatin, limiting its ability to capture the dynamic nature of chromatin. In contrast, live-cell imaging experiments have demonstrated the dynamic nature of chromatin. To bridge the gap between the 3D genome structures and chromatin dynamics, we have developed a computational tool called PHi-C for interpreting Hi-C data as the dynamic 3D genome state in terms of polymer physics. PHi-C constructs a polymer model from an input Hi-C matrix. Analyzing a segment's dynamics reveals that it follows the generalized Langevin equation. Then, the segment's linear-response function relates to mean-square displacement. Thus, we established a theoretical approach to unveil the linear viscoelasticity of the 3D genome itself from Hi-C data or stochastic motion of a labeled locus.