Related Experiment Video

Updated: Oct 3, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

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FET fusion oncoproteins interact with BRD4 and SWI/SNF chromatin remodelling complex subtypes in sarcoma

Malin Lindén1, Christoffer Vannas1, Tobias Österlund1,2

  • 1Department of Laboratory Medicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, Institute of Biomedicine, University of Gothenburg, Sweden.

Molecular Oncology
|February 19, 2022
PubMed

Insights

FET fusion oncoproteins drive sarcoma and leukaemia by interacting with SWI/SNF complexes and BRD4. This interaction influences gene transcription, offering potential therapeutic targets for these cancers.

Area of Science:

  • Molecular Biology
  • Oncology
  • Chromatin Biology

Background:

  • FET fusion oncoproteins are hallmarks of over 20 sarcoma and leukaemia types.
  • These oncoproteins interact with the SWI/SNF chromatin remodelling complex, which has three subtypes: cBAF, PBAF, and GBAF/ncBAF.

Purpose of the Study:

  • To characterize the interactions between FET oncoproteins, SWI/SNF complexes, and the transcriptional coactivator BRD4.
  • To elucidate the molecular mechanisms underlying FET-fusion-induced oncogenic transcriptional profiles.

Main Methods:

  • Comprehensive biochemical analysis.
  • Chromatin immunoprecipitation sequencing.
  • Proteomic analysis.

Main Results:

  • FET oncoproteins bind to all three main SWI/SNF subtypes.
  • FET oncoproteins interact indirectly with BRD4 through SWI/SNF.
  • FET oncoproteins, SWI/SNF components, and BRD4 co-localize on chromatin and interact with mediator and RNA Polymerase II.

Conclusions:

  • A molecular mechanism for FET-fusion-driven oncogenic transcription is proposed.
  • Aberrant SWI/SNF complexes and/or BRD4 may represent novel therapeutic targets in FET-fusion-related malignancies.
Keywords:
BAFBRD4EWSR1-FLI1FUS-DDIT3SWI/SNFSarcoma

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