| Abstract |
Capillary forces are driven by interactions between liquids and surfaces1. These forces are crucial for many processes ranging from biology and physics to engineering, such as the motion of aquatic insects on the surface of water2, modulation of the material properties of spider silk3,4, and self-assembly of small objects and microstructures5. Recent studies have shown that cells assemble biomolecular condensates in a manner similar to phase separation6. In the nucleus, these condensates are thought to drive transcription7–10, heterochromatin formation11,12, nucleolus assembly13,14, and DNA repair15,16. Here, we test if the interaction between liquid-like condensates and chromatin generates capillary forces, which 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, and theory to show that the pioneer transcription factor FoxA1 mediates the condensation of a DNA-protein phase via a mesoscopic first-order phase transition. Surprisingly, after nucleation, capillary 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 using capillary forces. Our work suggests that the physics of DNA and protein condensation driven by capillary forces provides a general regulatory principle for chromatin organization. |