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Updated: Jan 17, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
FET fusion oncoproteins enrich SWI/SNF complex subtypes and interaction partners
Malin Lindén1, Lisa Andersson1, Heba Albatrok1
1Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Background:
FET (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.
Methods:
We 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.
Results:
Our 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.
Conclusions:
These 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.
Insights
FET oncoproteins interact with SWI/SNF complexes in sarcomas, influencing their composition and function. These interactions, along with epigenetic changes, contribute to specific tumor types in FET sarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- FET (FUS, EWSR1, TAF15) fusion oncoproteins are key in sarcomas and leukemias.
- FET oncoproteins interact with SWI/SNF chromatin remodeling complex subtypes.
- The precise impact on SWI/SNF composition and epigenetic effects is not fully understood.
Purpose of the Study:
- To investigate how FET oncoproteins affect SWI/SNF complex composition and interactomes.
- To determine the downstream epigenetic consequences in FET sarcomas.
Main Methods:
- Utilized immunoprecipitation and quantitative mass spectrometry.
- Validated complex composition and interactions using glycerol gradient sedimentation and co-immunofluorescence.
- Analyzed chromatin accessibility (ATAC-seq) and gene regulation (RNA-seq) in FET sarcomas.
Main Results:
- FET sarcomas exhibit distinct SWI/SNF complex compositions with unique subunit paralogs and interaction partners.
- FET oncoproteins do not significantly disrupt SWI/SNF complex integrity.
- FUS::DDIT3-bound SWI/SNF complexes in myxoid liposarcoma are enriched in PBAF and GBAF components.
Conclusions:
- FET oncoproteins function with assembled, functional SWI/SNF complexes and recruited partners.
- SWI/SNF composition, interactomes, and epigenetics collectively influence FET sarcoma tumor type.
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