Fluidification of entangled polymers by loop extrusion

Filippo Conforto, Yair Gutierrez Fosado, Davide Michieletto
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引用次数: 0

Abstract

Loop extrusion is one of the main processes shaping chromosome organization across the cell cycle, yet its role in regulating deoxyribonucleic acid (DNA) entanglement and nucleoplasm viscoelasticity remains overlooked. We simulate entangled solutions of linear polymers under the action of generic loop extruding factors (LEFs) with a model that fully accounts for topological constraints and LEF-DNA uncrossability. We discover that extrusion drives the formation of bottlebrushlike structures which significantly lower the entanglement and effective viscosity of the system through an active fluidification mechanism. Interestingly, this fluidification displays an optimum at one LEF every 300–3000 base pairs. In marked contrast with entangled linear chains, the viscosity of extruded chains scales linearly with polymer length, yielding up to 1000-fold fluidification in our system. Our results illuminate how intrachain loop extrusion contributes to actively modulate genome entanglement and viscoelasticity in vivo.

Abstract Image

通过循环挤压使缠结聚合物流态化
环挤压是整个细胞周期中形成染色体组织的主要过程之一,但它在调节脱氧核糖核酸(DNA)缠结和核质粘弹性方面的作用仍被忽视。我们模拟了线性聚合物在通用环挤出因子(LEF)作用下的纠缠解,该模型充分考虑了拓扑约束和 LEF-DNA 不可交叉性。我们发现,挤压会推动形成瓶丛状结构,这种结构通过主动流化机制显著降低了系统的纠缠度和有效粘度。有趣的是,这种流化在每 300-3000 个碱基对就有一个 LEF 时显示出最佳状态。与缠结线性链形成鲜明对比的是,挤压链的粘度与聚合物长度成线性关系,在我们的系统中,流化程度可达 1000 倍。我们的研究结果阐明了链内环挤压是如何积极调节体内基因组缠结和粘弹性的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
8.60
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