Department of Physics and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States.
Elife. 2020 Dec 9;9:e63528. doi: 10.7554/eLife.63528.
Chromosome compaction is essential for reliable transmission of genetic information. Experiments suggest that ∼1000-fold compaction is driven by condensin complexes that extrude chromatin loops, by progressively collecting chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates that two-sided loop extrusion can achieve such compaction, but recent single-molecule studies (Golfier et al., 2020) observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, and two-sided extrusion. We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.
染色体的压缩对于遗传信息的可靠传递至关重要。实验表明，约 1000 倍的压缩是由 condensin 复合物驱动的，该复合物通过从复合物的一侧或两侧逐渐收集染色质纤维来形成不断增长的环。理论表明，双面环挤出可以实现这种压缩，但最近的单分子研究（Golfier 等人，2020）观察到 condensin 的多种动态，这些动态表现为单面、对称双面和双面挤出。我们使用模拟和理论来确定这些分子特性如何导致染色体压缩。如果即使一小部分 condensin 具有两个重要特性：长停留时间和进行双面（不一定对称）挤出的能力，那么就可以实现高压缩。在 condensin I 和 II 的混合物中，通过 condensin II 将双面挤出和稳定的染色质结合耦合起来，促进了压缩。这些结果提供了单分子观察和染色体尺度组织之间缺失的联系。
