Condensin Accelerates Long-Range Intra-Chromosomal Interactions

The 3D genome organization plays a key role in regulating interactions among chromosomal loci. While Chromosome Conformation Capture (3C)-based methods have provided static snapshots of chromatin architecture, the kinetics of chromosomal encounters in live cells remain poorly characterized. In this study, we employ Chemically Induced Chromosomal Interaction (CICI) to measure encounter times between multiple loci pairs in G1-arrested budding yeast. Our results show that chromosome motion closely follows the Rouse polymer model, with similar diffusion parameters at all tested loci. Surprisingly, we find that long-range intra-chromosomal encounters occur significantly faster than inter-chromosomal encounters at similar 3D distances. Using targeted depletion experiments, we identify condensin, but not cohesin, as the complex responsible for these rapid intra-chromosomal interactions. This is further supported by Hi-C analysis, which reveals that condensin promotes long-distance intra-chromosomal interactions in G1 yeast. Through polymer simulations, we estimate that condensin extrudes chromatin at ~2 kb/s with a density of one complex per 1-2 Mb and a processivity of 120-220 kb. These findings uncover a novel role for condensin in shaping the interphase genome organization and provide new insights into chromosomal search dynamics in vivo.3D基因组组织在调控染色体位点间的相互作用中发挥关键作用。基于染色体构象捕获（Chromosome Conformation Capture, 3C）的技术虽已为染色质架构提供了静态快照，但活细胞内染色体接触的动力学特征仍未得到充分阐释。本研究采用化学诱导染色体相互作用（Chemically Induced Chromosomal Interaction, CICI）技术，对G1期阻滞的出芽酵母中多个位点对的接触时间进行了测量。研究结果显示，染色体运动严格遵循Rouse聚合物模型，所有被测位点的扩散参数均较为相似。令人意外的是，在相近的三维距离条件下，长距离染色体内接触的发生速度显著快于染色体间接触。通过靶向缺失实验，我们鉴定出凝缩蛋白（condensin）而非黏连蛋白（cohesin）是介导这类快速染色体内相互作用的复合物。Hi-C分析进一步佐证了这一结论，该分析揭示凝缩蛋白可促进G1期酵母细胞内的长距离染色体内相互作用。通过聚合物模拟实验，我们估算出凝缩蛋白以约2 kb/s的速率挤出染色质，其复合物密度为每1-2 Mb一个，持续合成能力为120-220 kb。本研究揭示了凝缩蛋白在塑造间期基因组组织中的全新功能，并为体内染色体搜索动力学提供了新的见解。