|
| Status |
Public on Oct 21, 2014 |
| Title |
PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour types1. However, loss-of-function mutations in PRC2 components occur in a subset of haematopoietic malignancies, suggesting that this complex plays a dichotomous and poorly understood role in cancer2,3. Here we provide genomic, cellular, and mouse mod- elling data demonstrating that the polycomb group gene SUZ12 func- tions as tumour suppressor in PNS tumours, high-grade gliomas and melanomas by cooperating with mutations in NF1. NF1 encodes a Ras GTPase-activating protein (RasGAP) and its loss drives cancer by activating Ras4. We show that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras-driven transcription through effects on chromatin. Importantly, however, SUZ12 inactivation also triggers an epigenetic switch that sensitizes these cancers to bromodomain inhib- itors. Collectively, these studies not only reveal an unexpected con- nection between the PRC2 complex, NF1 and Ras, but also identify a promising epigenetic-based therapeutic strategy that may be exploited for a variety of cancers.
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| |
|
| Overall design |
2x3 samples (DMSO and PDJQ treated; WCL, BRD4 and H3K27Ac pulldown)
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| |
|
| Citation(s) |
25119042 |
| Submission date |
Oct 20, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Thomas De Raedt |
| E-mail(s) |
tderaedt@rics.bwh.harvard.edu
|
| Organization name |
Harvard Medical School - Brigham Women's Hospital
|
| Department |
Medicine
|
| Lab |
Cichowski Lab
|
| Street address |
77 Avenue Louis Pasteur
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (6)
|
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| This SubSeries is part of SuperSeries: |
| GSE52777 |
PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies |
|
| Relations |
| SRA |
SRP049051 |
| BioProject |
PRJNA264623 |
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