ArticleCellular & molecular biology letters2025
FET fusion oncoproteins enrich SWI/SNF complex subtypes and interaction partners.
Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundFET (FUS, EWSR1, and TAF15) fusion oncoproteins are characteristic for several sarcomas and leukemias, including myxoid liposarcoma and Ewing sarcoma. FET oncoproteins interact with the SWI/SNF chromatin remodeling complex subtypes cBAF, PBAF, and GBAF, but their impact on SWI/SNF compositions, interactions, and downstream epigenetic effects remains elusive.
methodsWe employ a comprehensive immunoprecipitation and quantitative mass spectrometry approach to determine the impact of FET oncoproteins on SWI/SNF composition and their interactomes. Validation of complex composition and interaction partners is performed by glycerol gradient sedimentation assays and co-immunofluorescence analysis. Furthermore, we determine the differential chromatin accessibility and gene regulation in FET sarcomas using assay for transposase-accessible chromatin sequencing and RNA sequencing, respectively.
resultsOur data show that FET sarcomas have distinct SWI/SNF complex compositions, with different subunit paralogs and subtype-specific components that utilize distinct sets of interaction partners, including specific transcription factors. We show that FET oncoproteins cause no major disruption of the SWI/SNF complex composition. Instead, FUS::DDIT3-bound SWI/SNF complexes in myxoid liposarcoma cells are enriched in PBAF and GBAF components as well as most interaction partners.
conclusionsThese data suggest that FET oncoproteins act together with fully assembled and functional SWI/SNF complexes and recruited interaction partners. Finally, our data reveal that the SWI/SNF compositions, interactomes, and epigenetic background contribute to the tumor type in FET sarcoma. Trial registration Clinical trial number: not applicable.
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