细胞生物学及生物物理学系Jan Ellenberg小组近日取得一项新成果。经过不懈努力，他们报道了纳米尺度DNA示踪揭示了有丝分裂染色体的自组织机制。2025年3月24日出版的《细胞》杂志发表了这项成果。

研究小组在单个分裂细胞中进行纳米级DNA追踪，以直接观察基因组DNA在有丝分裂期间从单环到整个染色体的三维折叠如何变化。他们的结构分析揭示了有丝分裂中具有6-8兆碱基的特征性基因组缩放。结合数据驱动模型和分子扰动，该研究团队可以表明，由凝聚形成的非常大且强烈重叠的环是有丝分裂染色体的基本结构原理。这些环在局部和全局上紧致染色体，达到染色质自排斥设定的极限。小组在3D中观察到的有丝分裂环的特征长度、密度和日益重叠的结构充分解释了细胞分裂过程中杆状有丝分裂染色体结构是如何通过自组织出现的。

据了解，基因组DNA如何在细胞分裂过程中折叠，形成具有特征的杆状有丝分裂染色体，这对忠实的基因组遗传至关重要，是生物学中一个长期悬而未决的问题。

附：英文原文

Title: Nanoscale DNA tracing reveals the self-organization mechanism of mitotic chromosomes

Author: Kai Sandvold Beckwith, Andreas Brunner, Natalia Rosalia Morero, Ralf Jungmann, Jan Ellenberg

Issue&Volume: 2025-03-24

Abstract: How genomic DNA is folded during cell division to form the characteristic rod-shaped mitotic chromosomes essential for faithful genome inheritance is a long-standing open question in biology. Here, we use nanoscale DNA tracing in single dividing cells to directly visualize how the 3D fold of genomic DNA changes during mitosis at scales from single loops to entire chromosomes. Our structural analysis reveals a characteristic genome scaling minimum of 6–8 megabases in mitosis. Combined with data-driven modeling and molecular perturbations, we can show that very large and strongly overlapping loops formed by condensins are the fundamental structuring principle of mitotic chromosomes. These loops compact chromosomes locally and globally to the limit set by chromatin self-repulsion. The characteristic length, density, and increasingly overlapping structure of mitotic loops we observe in 3D fully explain how the rod-shaped mitotic chromosome structure emerges by self-organization during cell division.

DOI: 10.1016/j.cell.2025.02.028

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00255-7