Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription

Abstract Abnormally formed FUS/EWS/TAF15 (FET) fusion oncoproteins are essential oncogenic drivers in many human cancers. Interestingly, at the molecular level, they also form biomolecular condensates specific loci. However, how these lead to gene transcription and features encoded DNA element regulate condensate formation remain unclear. Here, we develop an vitro single-molecule assay visualize phase separation on DNA. Using this technique, observe that FET proteins undergo target binding loci separated recruit RNA polymerase II enhance transcription. Furthermore, determine a threshold number of fusion-binding elements can protein condensates. These findings suggest oncoprotein promotes aberrant through loci-specific separation, which may contribute their transformation ability relevant cancers, such as sarcomas leukemia.