TY - JOUR T1 - Dynamic and Selective Low-Complexity Domain Interactions Revealed by Live-Cell Single-Molecule Imaging JF - bioRxiv DO - 10.1101/208710 SP - 208710 AU - Shasha Chong AU - Claire Dugast-Darzacq AU - Zhe Liu AU - Peng Dong AU - Gina M. Dailey AU - Claudia Cattoglio AU - Sambashiva Banala AU - Luke Lavis AU - Xavier Darzacq AU - Robert Tjian Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/05/16/208710.abstract N2 - Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity domains (LCDs) but how they perform transactivation functions remains unclear. Recent studies report that TF-LCDs can undergo hydrogel formation or liquid-liquid phase separation in vitro. Here, live-cell single-molecule imaging reveals 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 (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. These findings suggest that under physiological conditions, rapid reversible and multivalent LCD-LCD interactions occur between TFs and the Pol II machinery, which underpins a central mechanism for transactivation and plays a key role in gene expression and disease. ER -