Interactions between liquids and surfaces generate forces^1,2 that are crucial for many processes in biology, physics and engineering, including the motion of insects on the surface of water³, modulation of the material properties of spider silk⁴ and self-assembly of microstructures⁵. Recent studies have shown that cells assemble biomolecular condensates via phase separation⁶. In the nucleus, these condensates are thought to drive transcription⁷, heterochromatin formation⁸, nucleolus assembly⁹ and DNA repair¹⁰. 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 protein–DNA 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 into close proximity, suggesting that this physical mechanism is a possible general regulatory principle for chromatin organization that may be relevant in vivo.

液体和表面之间的相互作用产生的力^1,2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³上的运动、蜘蛛丝材料特性的调节⁴和微结构的自组装⁵ . 最近的研究表明，细胞通过相分离⁶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⁷、异染色质形成⁸、核仁组装⁹和 DNA 修复¹⁰. 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可能在将 DNA 的远距离调节元件结合在一起中发挥作用，这是转录调节的关键步骤。我们结合定量显微镜、体外重组、光镊和理论来证明转录因子 FoxA1 通过介观一级相变介导蛋白质-DNA 相的凝聚。成核后，共缩合力通过拉动未缩合的 DNA 来推动这一阶段的生长。改变 DNA 链上的张力会扩大或溶解凝聚物，从而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 凝聚可以使遥远的 DNA 区域靠近，