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| Status |
Public on Jan 10, 2012 |
| Title |
Notch1-driven epigenetic changes in a mouse model of T cell Acute Lymphoblastic Leukemia (T-ALL) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we used a mouse model of T-ALL through the overexpression of the intarcellular transcriptionally active part of Notch1 (N1-IC). This model faithfully recapitulates the major characteristics of the human disease. Comparison of the leukemic cells from peripheral tumors(thymoma) of this mouse model to normal thymic cells Double Positive (DP) for the markers CD4 and CD8 that express very low levels of Notch1 showed major expression changes (please see GSE34554) in pathways controlling the transition from physiology to disease. Further correlation of the data to ChIP-Seq data from the same cell populations led us to identify a hitherto unknown antagonism of the Notch1 oncogenic pathway and the polycomb complex (PRC2) in leukemia. Importantly exome sequencing in primary samples from human patients with T-ALL revealed that the PRC2 complex is frequently mutated and inactivated, further supporting the tumor suppressor role of the complex in this disease.
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| Overall design |
Gene expression profiles from CD4+/8+ Double Positive (named DP) derived from normal thymus and Notch1-IC over-expressing tumors (named T-ALL) were analyzed for the genomewide enrichments of two major activating epigenetic marks (Histone 3 Lysine 9 acetylation (H3K9ac) and lysine 4 trimethylation (H3K4me3)), one reprressive mark (Histone 3 lysine 27 trimethylation, H3K27me3) and the major oncogene Notch1.
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| Contributor(s) |
Tsirigos A, Ntziachristos P |
| Citation(s) |
22237151 |
| Submission date |
Jan 09, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Aristotelis Tsirigos |
| E-mail(s) |
atsirigo@us.ibm.com
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| Organization name |
IBM Research
|
| Department |
Computational Biology Center
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| Lab |
Computational Genomics
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| Street address |
1101 Kitchawan Road, Route 134
|
| City |
Yorktown Heights |
| State/province |
NY |
| ZIP/Postal code |
10598 |
| Country |
USA |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (18)
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| Relations |
| SRA |
SRP010188 |
| BioProject |
PRJNA150959 |
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