Force generation by protein–DNA co-condensation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Thomas Quail - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology (Author)
  • Stefan Golfier - , Clusters of Excellence PoL: Physics of Life, Chair of Biomimetic Materials, Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD) (Author)
  • Maria Elsner - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology (Author)
  • Keisuke Ishihara - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology (Author)
  • Vasanthanarayan Murugesan - , Clusters of Excellence PoL: Physics of Life, Chair of BioNano-Tools, Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD) (Author)
  • Roman Renger - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Frank Jülicher - , Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD), TUD Dresden University of Technology (Author)
  • Jan Brugués - , Clusters of Excellence PoL: Physics of Life, Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems, Center for Systems Biology Dresden (CSBD) (Author)

Abstract

Interactions between liquids and surfaces generate forces1,2 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.

Details

Original languageEnglish
Pages (from-to)1007-1012
Number of pages6
JournalNature physics
Volume17
Issue number9
Publication statusPublished - Sept 2021
Peer-reviewedYes

Keywords

ASJC Scopus subject areas