Imaging dynamic and selective low-complexity domain interactions that control gene transcription

Science. 2018 Jul 27;361(6400):eaar2555. doi: 10.1126/science.aar2555. Epub 2018 Jun 21.


Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA-Binding Proteins / chemistry*
  • Genes, Synthetic
  • Humans
  • Operator Regions, Genetic
  • Protein Binding
  • Protein Interaction Domains and Motifs*
  • RNA Polymerase II / chemistry
  • Single Molecule Imaging / methods*
  • Transcription Factors / chemistry*
  • Transcription, Genetic*
  • Transcriptional Activation*


  • DNA-Binding Proteins
  • Transcription Factors
  • RNA Polymerase II