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| Status |
Public on Sep 05, 2018 |
| Title |
Chromatin state changes in HOXA9/MEIS1 leukemia cells [4C-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| 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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| Overall design |
Untransformed myeloid progenitors (MP), HOXA9/MEIS1-transformed myeloblasts (HMM cells) and HMM cells with HOXA9 inactivation were subjected to ChIP-seq, RNA-seq and 4C-seq for assessment of their chromatin states and transcriptomes. Untransformed pro-B cells and HOXA9/MEIS1-transformed proB lymphoblasts (HMB cells) were subjected to ChIP-seq for analysis of their chromatin states.
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| Contributor(s) |
Sun Y, Dou Y, Hess JL |
| Citation(s) |
30270123 |
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| Submission date |
Sep 05, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Yali Dou |
| E-mail(s) |
[email protected]
|
| Phone |
(734) 615-1315
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| Organization name |
University of Michigan
|
| Department |
Pathology Department
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| Lab |
5215 Medical Science Building I
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| Street address |
1301 Catherine Street
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE103508 |
HOXA9 Reprograms the Enhancer Landscape During Leukemic Transformation |
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| Relations |
| BioProject |
PRJNA401756 |
| SRA |
SRP117043 |
