FIGURE 5.

Proposed model for transcriptional reprogramming by FET‐fusion oncoproteins. Left: FET fusion proteins can bind to specific DNA motifs defined by the DNA‐binding domain at physiologically inactive genes to form phase‐separated condensates. The process of LLPS is facilitated by the prion‐like domain. FET oncofusion protein condensates can recruit the ATP‐dependent chromatin remodeler SWI/SNF leading to remodeling of the closed chromatin to an open chromatin state, which subsequently provides access to transcriptional coactivators and RNA polymerase II to mediate transcription of otherwise silenced genes. Right: The sequestration of chromatin remodeler SWI/SNF into FUS‐DDIT3 condensates, as shown in the left panel, can lead to diminished chromatin remodeling activity at physiologically active genes where continuous SWI/SNF activity is required. This sequestration of SWI/SNF away from the physiological target genes may trigger a switch to a closed chromatin state, thereby decreasing their transcriptional output