|
| Status |
Public on Oct 18, 2016 |
| Title |
Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a (ChIP-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Unlike clustered HOX genes, the role of non-clustered homeobox gene family members in hematopoiesis and leukemogenesis has not been extensively studied. Here we find that the Hematopoietically-expressed Homeobox gene, Hhex, is overexpressed in acute myeloid leukemia (AML) and is essential for the initiation and propagation of MLL-ENL induced AML, but dispensable for normal myelopoiesis, indicating a specific requirement for Hhex for leukemic growth. Loss of Hhex leads to upregulated expression of the tumor suppressors p16INK4a and p19ARF, which are required for growth arrest and myeloid differentiation following Hhex deletion. Mechanistically, we show that Hhex binds to the Cdkn2a locus and is required for H3K27Me3-mediated repression of this locus. Thus, Hhex is a novel therapeutic target that is specifically required for AML stem cells to repress tumor suppressor pathways and enable continued self-renewal.
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| |
|
| Overall design |
Genome-wide profiling of histone modification and Hhex binding in leukemia cells.
|
| |
|
| Contributor(s) |
Shields BJ, Shi W, Garnham AL, Smyth GK, McCormack MP |
| Citation(s) |
26728554 |
| Submission date |
Oct 14, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Wei Shi |
| E-mail(s) |
shi@wehi.edu.au
|
| Organization name |
The Walter and Eliza Hall Institute of Medical Research
|
| Department |
Bioinformatics
|
| Street address |
1G Royal Parade
|
| City |
Parkville |
| State/province |
Victoria |
| ZIP/Postal code |
3050 |
| Country |
Australia |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (9)
|
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| This SubSeries is part of SuperSeries: |
| GSE74019 |
Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a |
|
| Relations |
| BioProject |
PRJNA298747 |
| SRA |
SRP064810 |
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