Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma [ChIP-Seq]

  • Bao Han T Vo (Contributor)
  • Chunliang Li (Contributor)
  • Marc Alard Morgan (Contributor)
  • Ilan Theurillat (Contributor)
  • David Finkelstein (Contributor)
  • Shaela Wright (Contributor)
  • Judith Hyle (Contributor)
  • Stephanie M.C. Smith (Contributor)
  • Yiping Fan (Contributor)
  • Yong Dong Wang (Contributor)
  • Gang Wu (Contributor)
  • Brent A. Orr (Contributor)
  • Paul A. Northcott (Contributor)
  • Ali Shilatifard (Contributor)
  • Charles J. Sherr (Contributor)
  • Martine F. Roussel (Contributor)

Dataset

Description

Accession Number: GSE84761

Platform:
GPL16417: Illumina MiSeq (Mus musculus)

Organism: Mus musculus

Published on 2017-03-01

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

Contact:
Name: David Finkelstein
Organization: St Jude Children's Research Hospital
Deparment: Computational Biology
Address: 332 N. Lauderdale St. Memphis TN 38105 USA
Email: david.finkelstein@stjude.org
Phone: 9014953931

Organization: GEO
Address: USA
Date made available2017
PublisherGene Expression Omnibus

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