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| Status |
Public on Dec 19, 2013 |
| Title |
RNAseq of PRMT4KD in human cord blood derived CD34+ cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Defining the role of epigenetic regulators in normal hematopoiesis has become critically important, as recurrent mutations or aberrant expression of these genes has been identified in both myeloid and lymphoid hematological malignancies. We have found that PRMT4, a type I arginine methyltransferase, whose function in normal and malignant hematopoiesis is unknown, is overexpressed in AML patient samples. In support of an oncogenic role for PRMT4, we find that its overexpression blocks the myeloid differentiation of human stem/progenitor cells (HSPCs) while its knockdown (KD) is sufficient to induce myeloid differentiation of HSPCs and multiple AML cell lines. Although classically thought of as a co-activator, we found that PRMT4 functions to repress the expression of miR-223 in HSPCs via the methylation of RUNX1, which triggers the assembly of a multi-protein repressor complex that includes DPF2. As part of a feedback loop, PRMT4 expression is repressed post-transcriptionally by miR-223 during the normal differentiation process. These data reveal an unidentified role of PRMT4 in myeloid differentiation and its unexpected repressive role in transcriptional regulation. Furthermore, depletion of PRMT4 results in the differentiation of myeloid leukemia cells in vitro and their decrease proliferation in vivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia.
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| Overall design |
Purified human primary CD34+ cells were transduced with lentiviruses carrying PRMT4KD or scramble control shRNAs. Total RNA was extrated. RNAseq was performed to identify target genes that are regulated by PRMT4. Experiments were performed in triplicate.
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| Contributor(s) |
Vu L, Nimer S |
| Citation(s) |
24332853 |
| Submission date |
Apr 15, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Bic MSKCC |
| Organization name |
Memorial SLoan-Kettering Cancer Center
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| Street address |
1275 York Ave.
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA197140 |
| SRA |
SRP021085 |
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