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| Status |
Public on Oct 17, 2019 |
| Title |
NPM and NPM-MLF1 interact with chromatin remodeling complexes and influence their recruitment to specific genes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Nucleophosmin (NPM1) is either frequently mutated or subjected to chromosomal translocation in acute myeloid leukemia (AML). NPM protein is primarily located in the nucleus, but the recurrent NPMc+ mutation is characterized by cytoplasmic localization and leukemogenic properties. Similarly, the NPM-MLF1 translocation product favors the partial cytoplasmic retention of NPM. Regardless of their common cellular distribution, NPM-MLF1 malignancies engender different effects on hematopoiesis compared to NPMc+ counterparts, highlighting possible aberrant nuclear function(s) of NPM in NPMc+ AML. We performed a proteomics analysis and found that NPM and NPM-MLF1 interact with chromatin remodeling complexes of the ISWI family, as well as with NuRD and P/BAF complexes. Accordingly, NPM and NPM-MLF1 are recruited to transcriptionally active or repressed genes along with NuRD and P/BAF elements. Although the overall gene expression program in NPM knockdown cells is similar to that resulting from NPMc+ and is consistent with loss of nuclear function of NPM, NPM-MLF1 expression differentially altered gene transcription regulated by NPM. The abnormal gene regulation imposed by NPM-MLF1 is characterized by enhanced recruitment of NuRD to gene regulatory regions. Thus, different mechanisms orchestrate the deregulation of NPM function in NPMc+- versus NPM1-MLF1-associated leukemia.
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| Overall design |
Gene expression profil was determinated by Ion Ampli Sequencing in K562 sh Scramble (contrôle) and K562 shNPM cells, in triplicate.
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| Contributor(s) |
Milot E |
| Citation(s) |
31675375 |
| Submission date |
Dec 29, 2018 |
| Last update date |
Dec 05, 2019 |
| Contact name |
Eric Milot |
| E-mail(s) |
e.milot.06@gmail.com, e.milot.1@umontreal.ca
|
| Phone |
514 252 3551
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| Organization name |
HMR research center/Université de Montréal
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| Department |
Medicine
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| Lab |
JADS 2nd floor
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| Street address |
5415 boul. l'Assomption
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| City |
Montréal |
| State/province |
Québec |
| ZIP/Postal code |
H1T 2M4 |
| Country |
Canada |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA512203 |
| SRA |
SRP174885 |
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