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凝缩蛋白加速染色体内部的长程相互作用。

Condensin Accelerates Long-Range Intra-Chromosomal Interactions.

作者信息

Zou Fan, Li Yi, Földes Timothy, Pinholt Henrik Dahl, Smith Courtney, Mirny Leonid, Bai Lu

机构信息

Department of Physics, The Pennsylvania State University, University Park, PA 16802, USA.

Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.

出版信息

bioRxiv. 2025 May 3:2025.05.02.651983. doi: 10.1101/2025.05.02.651983.

Abstract

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 .

摘要

三维基因组组织在调节染色体位点间的相互作用中起关键作用。虽然基于染色体构象捕获(3C)的方法提供了染色质结构的静态快照,但活细胞中染色体相遇的动力学仍知之甚少。在本研究中,我们采用化学诱导染色体相互作用(CICI)来测量G1期停滞的芽殖酵母中多个位点对之间的相遇时间。我们的结果表明,染色体运动紧密遵循劳斯聚合物模型,在所有测试位点具有相似的扩散参数。令人惊讶的是,我们发现在相似的三维距离下,远距离染色体内相遇比染色体间相遇发生得明显更快。通过靶向缺失实验,我们确定凝聚素而非黏连蛋白是负责这些快速染色体内相互作用的复合物。这进一步得到了Hi-C分析的支持,该分析表明凝聚素促进G1期酵母中的远距离染色体内相互作用。通过聚合物模拟,我们估计凝聚素以约2 kb/s的速度挤压染色质,每1 - 2 Mb有一个复合物,持续长度为120 - 220 kb。这些发现揭示了凝聚素在塑造间期基因组组织中的新作用,并为染色体搜索动力学提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db0c/12247638/5606541497b5/nihpp-2025.05.02.651983v1-f0001.jpg

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