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| Status |
Public on May 13, 2016 |
| Title |
An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
B-cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase, but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic EZH2 gain-of-function mutation (Y646F in human, Y641F in the mouse) can be conditionally expressed. Expression of Ezh2Y641F in mouse B-cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Bcl2 overexpression or p53 loss, but not c-Myc overexpression, further accelerated lymphoma progression, and expression of mutant B-Raf but not mutant N-Ras further accelerated melanoma progression. Although expression of Ezh2Y641F increased abundance of global H3K27 trimethylation (H3K27me3), it also caused a widespread redistribution of this repressive mark, including a loss of H3K27me3 associated with increased transcription at many loci. These results suggest that Ezh2Y641F induces lymphoma and melanoma through a vast reorganization of chromatin structure inducing both repression and activation of polycomb-regulated loci.
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| Overall design |
B cells: 4 WT vs 4 Y641F samples, Melanoma: WT (480, 855) vs Y641F (480D, 855D) isogenic cell lines differing only for the presence of WT vs Y641F Ezh2.
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| |
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| Contributor(s) |
Souroullas GP, Parker JS, Jeck WR |
| Citation(s) |
27135738 |
| Submission date |
Mar 09, 2016 |
| Last update date |
Sep 10, 2021 |
| Contact name |
George P. Souroullas |
| E-mail(s) |
George.souroullas@wustl.edu
|
| Organization name |
Washington University School of Medicine
|
| Department |
Medicine
|
| Lab |
Souroullas
|
| Street address |
660 S. Euclid Av
|
| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE79036 |
An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome |
|
| Relations |
| BioProject |
PRJNA314772 |
| SRA |
SRP071338 |
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