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Series GSE62499 Query DataSets for GSE62499
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.
Overall design 2x3 samples (DMSO and PDJQ treated; WCL, BRD4 and H3K27Ac pulldown)
Citation(s) 25119042
Submission date Oct 20, 2014
Last update date May 15, 2019
Contact name Thomas De Raedt
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)
GSM1527926 DMSO_BRD4_ChIPseq
GSM1527927 DMSO_H3K27Ac_ChIPseq
GSM1527928 DMSO_input
This SubSeries is part of SuperSeries:
GSE52777 PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies
SRA SRP049051
BioProject PRJNA264623

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62499_RAW.tar 2.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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