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| Status |
Public on Nov 01, 2021 |
| Title |
Next generation sequencing of RNA of MLL-AF9-139 cells treated with and without Doxycycline |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
MIR139 is a tumor suppressor and commonly silenced in Acute myeloid leukemia (AML). Reactivating the expression of MIR139 eliminates AML cells. Here, we investigated the mechanism of MIR139 gene inactivation in AML expressing the Mixed-Lineage Leukemia (MLL)-AF9 oncogene. We found that MLL-AF9-mediated repression of MIR139 is a selective event in leukemogenesis. Analyses of Histone marks revealed two well-conserved enhancer regions, which are epigenetically silenced by the Polycomb-Repressive Complex-2 (PRC2) downstream of MLL-AF9. Genomic deletion of these enhancer regions abolished transcriptional regulation of MIR139. Genome-wide knockout screens revealed the transcriptional pausing factor of RNA Polymerase-II, POLR2M, as a critical MIR139 silencing factor. Furthermore, POLR2M-binding to the MIR139 transcriptional start site induces paused transcription, which is abrogated upon PRC2 inhibition. Together, we present evidence for a POLR2M-mediated MIR139 silencing mechanism, downstream of MLL-AF9 and PRC2. The findings in this study highlight the importance of the transcriptional deregulation in malignant transformation.
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| Overall design |
RNAs-seq of 3 MLL-AF9-i139 and 1 MLL-AF9-ieGFP clones treated with Doxycycline and 3 MLL-AF9-i139 and 1 MLL-AF9-ieGFP clones treated without Doxycycline
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| |
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| Contributor(s) |
Erkeland SJ, Stavast CJ |
| Citation(s) |
34741119 |
| |
| Submission date |
Oct 29, 2020 |
| Last update date |
Jan 31, 2022 |
| Contact name |
Stefan J. Erkeland |
| Organization name |
Erasmus University Medical Center
|
| Department |
Department of Immunology
|
| Lab |
Non-Coding RNA and Leukemia
|
| Street address |
Dr. Molewaterplein 40
|
| City |
Rotterdam |
| State/province |
Zuid-Holland |
| ZIP/Postal code |
3015GD |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE160406 |
Next generation sequencing of WT or Mir139KO MLL-AF9 cells |
|
| Relations |
| BioProject |
PRJNA673306 |
| SRA |
SRP290294 |
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