|
| Status |
Public on Sep 05, 2018 |
| Title |
RNA expression changes in HOXA9/MEIS1 leukemia cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Aberrant expression of homeobox transcription factor HOXA9 is a central component of the leukemogenic program driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid progenitor cells and pro-B cells leads to significant rearrangement of the epigenetic landscape with prominent emergence of cancer specific de novo enhancers. HOXA9 acts as a pioneer factor at the de novo enhancers and is required for recruitment of transcription factor CEBP/a and the histone H3K4 methyltransferase MLL3/MLL4 complex. HOXA9 function at the de novo enhancer is distinct from its physiological role at distal enhancers during normal hematopoietic development. Genetic deletion of MLL3/4 specifically affects the active enhancer signatures at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis. Our study reveals a previously uncharacterized role of HOXA9 and the MLL3/4 complex in leukemogenesis and provide mechanistic insights in epigenetic deregulation during malignant transformation.
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| |
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| Overall design |
RNA-seq for untransformed myeloid progenitors (MP)
|
| |
|
| Contributor(s) |
Sun Y, Dou Y, Hess JL |
| Citation(s) |
30270123 |
| |
| Submission date |
Sep 05, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Yali Dou |
| E-mail(s) |
[email protected]
|
| Phone |
(734) 615-1315
|
| Organization name |
University of Michigan
|
| Department |
Pathology Department
|
| Lab |
5215 Medical Science Building I
|
| Street address |
1301 Catherine Street
|
| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (2) |
|
| This SubSeries is part of SuperSeries: |
| GSE103508 |
HOXA9 Reprograms the Enhancer Landscape During Leukemic Transformation |
|
| Relations |
| BioProject |
PRJNA401757 |
| SRA |
SRP117042 |
