PRMT4 blocks myeloid differentiation by assembling a Methyl-RUNX1-dependent repressor complex Journal Article

Authors: Vu, L. P.; Perna, F.; Wang, L.; Voza, F.; Figueroa, M. E.; Tempst, P.; Erdjument-Bromage, H.; Gao, R.; Chen, S.; Paietta, E.; Deblasio, T.; Melnick, A.; Liu, Y.; Zhao, X.; Nimer, S. D.
Article Title: PRMT4 blocks myeloid differentiation by assembling a Methyl-RUNX1-dependent repressor complex
Abstract: Defining the role of epigenetic regulators in hematopoiesis has become critically important, because recurrent mutations or aberrant expression of these genes has been identified in both myeloid and lymphoid hematological malignancies. We found that PRMT4, a type I arginine methyltransferase whose function in normal and malignant hematopoiesis is unknown, is overexpressed in acute myelogenous leukemia patient samples. Overexpression of PRMT4 blocks the myeloid differentiation of human stem/progenitor cells (HSPCs), whereas its knockdown is sufficient to induce myeloid differentiation of HSPCs. We demonstrated that PRMT4 represses the expression of miR-223 in HSPCs via the methylation of RUNX1, which triggers the assembly of a multiprotein repressor complex that includes DPF2. As part of the feedback loop, PRMT4 expression is repressed posttranscriptionally by miR-223. Depletion of PRMT4 results in differentiation of myeloid leukemia cells invitro and their decreased proliferation invivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia. © 2013 The Authors.
Journal Title: Cell Reports
Volume: 5
Issue: 6
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2013-12-26
Start Page: 1625
End Page: 1638
Language: English
DOI: 10.1016/j.celrep.2013.11.025
PROVIDER: scopus
PUBMED: 24332853
PMCID: PMC4073674
Notes: Export Date: 3 February 2014 -- Source: Scopus
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MSK Authors
  1. Paul J Tempst
    307 Tempst
  2. Stephen D Nimer
    345 Nimer
  3. Xinyang Zhao
    29 Zhao
  4. Fabiana Perna
    45 Perna
  5. Lan Wang
    14 Wang
  6. Ly P Vu
    30 Vu
  7. Francesca Alexandra Voza
    18 Voza