Single-Moelecule Imaging Of Fet Fusion Oncoproteins

FET fusion proteins (FUS/EWS/TAF15) are critical in many human cancers, like sarcomas and leukemia. Interestingly, at the molecular level, they also form biomolecular condensates. However, the underlying biophysical mechanism of these condensates on DNA remains poorly understood. Studies using single-molecule method, DNA Curtains, demonstrated that FET fusion proteins form finite sized droplets on DNA via liquid-liquid phase separation. They bind strongly to loci with a threshold number of binding sites. Importantly, the C-terminal domain of RNA polymerase II can be also recruited to these specific loci with a threshold number of binding sites to enhance gene transcription, suggesting a mechanism for biomolecular condensates -mediated dysregulation of gene expression during tumorigenesis. These findings have important implications for understanding the relationship between transcription regulation and cancer onset.