Interactions between liquids and surfaces generate forces that are crucial for many processes in biology, physics, and engineering, including the motion of insects on the surface of water, modulation of the material properties of spider silk, and self-assembly of microstructures. Recent studies have shown that cells assemble biomolecular condensates via phase separation. In the nucleus, these condensates are thought to drive transcription, heterochromatin formation, nucleolus assembly, and DNA repair. Here, we show that the interaction between liquid-like condensates and DNA generates forces that might play a role in bringing distant regulatory elements of DNA together, a key step in transcriptional regulation. We combine quantitative microscopy, in vitro reconstitution, optical tweezers, and theory to show that the transcription factor FoxA1 mediates the condensation of a DNA-protein phase via a mesoscopic first-order phase transition. After nucleation, co-condensation forces drive growth of this phase by pulling non-condensed DNA. Altering the tension on the DNA strand enlarges or dissolves the condensates, revealing their mechanosensitive nature. These findings show that DNA condensation mediated by transcription factors could bring distant regions of DNA in close proximity, suggesting that this physical mechanism is a possible general regulatory principle for chromatin organization that may be relevant in vivo.

中文翻译：

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通过蛋白质-DNA 共缩合产生力

液体和表面之间的相互作用产生的力对生物学、物理学和工程学中的许多过程至关重要，包括昆虫在水面上的运动、蜘蛛丝材料特性的调节以及微结构的自组装。最近的研究表明，细胞通过相分离组装生物分子凝聚物。在细胞核中，这些凝聚物被认为驱动转录、异染色质形成、核仁组装和 DNA 修复。在这里，我们表明液体状凝聚物和 DNA 之间的相互作用产生的力量可能在将 DNA 的远处调控元件聚集在一起方面发挥作用，这是转录调控的关键步骤。我们结合了定量显微镜、体外重组、光镊、和理论表明转录因子 FoxA1 通过介观一级相变介导 DNA-蛋白质相的凝聚。成核后，共缩合力通过拉动未缩合的 DNA 来推动该阶段的生长。改变 DNA 链上的张力会扩大或溶解凝聚物，揭示它们的机械敏感性。这些发现表明，由转录因子介导的 DNA 缩合可以使 DNA 的远处区域靠近，这表明这种物理机制可能是染色质组织的一般调控原理，可能与体内相关。改变 DNA 链上的张力会扩大或溶解凝聚物，揭示它们的机械敏感性。这些发现表明，由转录因子介导的 DNA 缩合可以使 DNA 的远距离区域靠近，这表明这种物理机制可能是染色质组织的一般调控原理，可能与体内相关。改变 DNA 链上的张力会扩大或溶解凝聚物，揭示它们的机械敏感性。这些发现表明，由转录因子介导的 DNA 缩合可以使 DNA 的远距离区域靠近，这表明这种物理机制可能是染色质组织的一般调控原理，可能与体内相关。