Force generation by protein–DNA co-condensation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Thomas Quail - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD), Technische Universität Dresden (Autor:in)
  • Stefan Golfier - , Exzellenzcluster PoL: Physik des Lebens, Professur für Biomimetische Materialien, Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD) (Autor:in)
  • Maria Elsner - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD), Technische Universität Dresden (Autor:in)
  • Keisuke Ishihara - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD), Technische Universität Dresden (Autor:in)
  • Vasanthanarayan Murugesan - , Exzellenzcluster PoL: Physik des Lebens, Professur für BioNano-Werkzeuge, Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD) (Autor:in)
  • Roman Renger - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Frank Jülicher - , Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD), Technische Universität Dresden (Autor:in)
  • Jan Brugués - , Exzellenzcluster PoL: Physik des Lebens, Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD) (Autor:in)

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

OriginalspracheEnglisch
Seiten (von - bis)1007-1012
Seitenumfang6
FachzeitschriftNature physics
Jahrgang17
Ausgabenummer9
PublikationsstatusVeröffentlicht - Sept. 2021
Peer-Review-StatusJa

Schlagworte

ASJC Scopus Sachgebiete