Kinetic organization of the genome revealed by ultraresolution multiscale live imaging

• 成果类型: Article
• 署名作者: Lee, Joo; Chen, Liang-Fu; Gaudin, Simon; Gupta, Kavvya; Novacic, Ana; Spakowitz, Andrew; Boettiger, Alistair Nicol
• 署名单位: Stanford University; Stanford University; Stanford University; Roche Holding; Roche Holding USA; Genentech
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13755
• DOI: 10.1126/science.adx2202
• 发表日期: 2025-09-18
• 关键词: 3d genome; chromosome conformation; dna; transcription; diffusion; repressor; DYNAMICS; Visualization; mechanisms; principles

摘要

Genome function requires regulated genome motion. However, tools to directly observe this motion in vivo have been limited in coverage and resolution. Here we introduce an approach to tile mammalian chromosomes with self-mapping fluorescent labels and track them at ultraresolution. We find that sequences separated by submegabase distances transition to proximity in tens of seconds. This rapid search is dependent on cohesin and is exhibited only within domains. Domain borders act as kinetic impediments to this search process, rather than structural boundaries. The genomic separation-dependent scaling of the search time for cis interactions violated predictions of diffusion, suggesting motor-driven folding. We also uncover cohesin-dependent processive motion at 2.7 kilobases per second. Together, these multiscale dynamics reveal the organization of the genome into kinetically associated domains.