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| Status |
Public on Feb 01, 2016 |
| Title |
H3K27 methylation changes in Jurkat cells in response to TAL1-KD |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
T-cell Acute Lymphoblastic Leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and as such T-ALL treatments are uniformly applied across subtypes leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL whereby a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in dosage and activity of the histone 3 lysine 27 (H3K27) demethylase UTX. Specifically, we identify UTX as a co-activator of TAL1. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a potent oncogene essential for maintaining the leukemic phenotype of TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we designed a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that is highly effective against TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients.
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| Overall design |
H3K27me3 ChIP-seq in two conditions (Wt and TAL1-KD), and one input sample (no replicates).
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| Contributor(s) |
Brand M, Benyoucef A, Porter CJ |
| Citation(s) |
26944678 |
| |
| Submission date |
Aug 24, 2015 |
| Last update date |
May 15, 2019 |
| Organization |
Ottawa Hospital Research Institute |
| Phone |
(613) 737-8899 -73255
|
| Department |
Cellular and Molecular Medicine
|
| Lab |
Ottawa Bioinformatics Core Facility
|
| Street address |
501 Smyth Rd.
|
| City |
Ottawa |
| State/province |
ON |
| ZIP/Postal code |
K1H 8L6 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE72300 |
T-cell ALL in response to TAL1-KD, UTX-KD, and GSKJ4 treatment |
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| Relations |
| BioProject |
PRJNA293696 |
| SRA |
SRP062774 |
