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Series GSE59427 Query DataSets for GSE59427
Status Public on Oct 01, 2015
Title Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis
Organism Mus musculus
Experiment type Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
Summary Alterations of chromatin modifiers are frequent in cancer but their functional consequences remain often unclear. Focusing on the Polycomb protein EZH2 that deposits H3K27me3 mark, we showed that its high expression in solid tumors is a consequence, and not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process is malfunctioning in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes are actually of poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes consequent to EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.

 
Overall design Refer to individual Series
 
Citation(s) 26637281
Submission date Jul 15, 2014
Last update date May 15, 2019
Contact name Nicolas Servant
E-mail(s) Nicolas.Servant@curie.fr
Organization name Institut Curie
Street address 26 rue d'ulm
City Paris Cedex 05
ZIP/Postal code 75248
Country France
 
Platforms (3)
GPL11533 [MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version]
GPL16790 AB 5500 Genetic Analyzer (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (30)
GSM1432927 Exp1 C2 iMEFs Ezh2 WT/WT
GSM1432928 Exp1 C2 iMEFs Ezh2 WT/WT, replicate 1
GSM1432929 Exp1 C2 iMEFs Ezh2 WT/WT, replicate 2
This SuperSeries is composed of the following SubSeries:
GSE59293 Genome-wide analysis of H3K27me3 in Ezh2-conditional iMEFs
GSE59346 Expression data from Ezh2 conditional C2 iMEFs
Relations
BioProject PRJNA255297

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
GSE59427_RAW.tar 1.7 Gb (http)(custom) TAR (of BED, BIGWIG, CEL)
SRA Run SelectorHelp
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