| Autor: |
Nicolas L. Fawzi, Izzy Owen, Debra S. Yee, Victoria Johnson, Robert L. Kortum, Theodora Myrto Perdikari, Jeremy T. Smyth, Frank Shewmaker, Hala Wyne |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.02.24.432743 |
| Popis: |
Myxoid liposarcoma is caused by a chromosomal translocation resulting in a fusion protein comprised of the N-terminus of FUS (fused in sarcoma) and the full-length transcription factor CHOP (CCAAT/Enhancer Binding Protein Homologous Protein). FUS functions in RNA metabolism and CHOP is a stress-induced transcription factor. The FUS-CHOP fusion protein causes unique gene expression and oncogenic transformation. The FUS segment is required for oncogenic transformation, but the mechanism of FUS-CHOP-induced transcriptional activation is unknown. Recently, some transcription factors and super enhancers were proposed to undergo liquid-liquid phase separation and form membraneless compartments that recruit transcription machinery to gene promoters. Since phase separation of FUS depends on its N-terminus, transcriptional activation by FUS-CHOP could result from the N-terminus driving nuclear phase transitions. Here, we characterized FUS-CHOP in cells and in vitro, and observed novel phase-separating properties relative to unmodified CHOP. Our data indicate FUS-CHOP forms phase-separated condensates at super enhancer transcriptional sites. We provide strong evidence that the FUS-CHOP phase transition is a novel oncogenic mechanism and potential therapeutic target for treatment of myxoid liposarcoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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