Format

Send to

Choose Destination
EMBO Rep. 2019 Apr 8. pii: e45766. doi: 10.15252/embr.201845766. [Epub ahead of print]

FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex.

Author information

1
Department of Pathology and Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2
Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden.
3
Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
4
Department of Pathology and Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden anders.stahlberg@gu.se pierre.aman@gu.se.
5
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.

Abstract

Members of the human FET family of RNA-binding proteins, comprising FUS, EWSR1, and TAF15, are ubiquitously expressed and engage at several levels of gene regulation. Many sarcomas and leukemias are characterized by the expression of fusion oncogenes with FET genes as 5' partners and alternative transcription factor-coding genes as 3' partners. Here, we report that the N terminus of normal FET proteins and their oncogenic fusion counterparts interact with the SWI/SNF chromatin remodeling complex. In contrast to normal FET proteins, increased fractions of FET oncoproteins bind SWI/SNF, indicating a deregulated and enhanced interaction in cancer. Forced expression of FET oncogenes caused changes of global H3K27 trimethylation levels, accompanied by altered gene expression patterns suggesting a shift in the antagonistic balance between SWI/SNF and repressive polycomb group complexes. Thus, deregulation of SWI/SNF activity could provide a unifying pathogenic mechanism for the large group of tumors caused by FET fusion oncoproteins. These results may help to develop common strategies for therapy.

KEYWORDS:

EWSR1‐FLI1; FET proteins; FUS‐DDIT3; SWI/SNF chromatin remodeling complex; fusion oncogenes

PMID:
30962207
DOI:
10.15252/embr.201845766
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center