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Series GSE84462 Query DataSets for GSE84462
Status Public on Mar 01, 2017
Title Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The most aggressive of four medulloblastoma (MB) subgroups are cMYC-driven Group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 trimethylase of polycomb repressive complex-2. Yet, engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression. Candidate oncogenic drivers upregulated following Ezh2 deletion included Gfi1, a proto-oncogene frequently activated in human G3 MBs. Gfi1 disruption antagonized the tumor promoting effects of Ezh2 loss; conversely, Gfi1 overexpression collaborated with Myc to bypass effects of Trp53 inactivation in primary cerebellar neuronal progenitors thereby driving MB progression. Although negative epigenetic regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects.
 
Overall design Mouse tumorspheres from a p53-/-;p18-/- or WT mixed background that is over-expressing Myc are transfected with a CAS9 vector to knockout Ezh2, or over express Ezh2, or overexpress Ezh2 to rescue a Ezh2 KO , or a vector that over expresses Gfi1
 
Contributor(s) Vo BT, Li C, Morgan M, Theurillat I, Finkelstein D, Wright S, Hyle J, Smith SM, Fan Y, Wang Y, Wu G, Orr BA, Northcott PA, Shilatifard A, Sherr CJ, Roussel MF
Citation(s) 28329683
Submission date Jul 15, 2016
Last update date May 15, 2019
Contact name David Finkelstein
E-mail(s) david.finkelstein@stjude.org
Phone 9014953931
Organization name St Jude Children's Research Hospital
Department Computational Biology
Street address 332 N. Lauderdale St.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (48)
GSM2236648 SJMMMB016795_X1-19251-Cas9-Tumor-rep1
GSM2236649 SJMMMB016795_X2-19251-Cas9-Tumor-rep2
GSM2236650 SJMMMB016795_X3-19251-Cas9-Tumor-rep3
This SubSeries is part of SuperSeries:
GSE84762 Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma
Relations
BioProject PRJNA329290
SRA SRP078594

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
GSE84462_RAW.tar 6.3 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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