TitlePRMT4 blocks myeloid differentiation by assembling a methyl-RUNX1-dependent repressor complex.
Publication TypeJournal Article
Year of Publication2013
AuthorsVu, Ly P., Perna Fabiana, Wang Lan, Voza Francesca, Figueroa Maria E., Tempst Paul, Erdjument-Bromage Hediye, Gao Rui, Chen Sisi, Paietta Elisabeth, Deblasio Tony, Melnick Ari, Liu Yan, Zhao Xinyang, and Nimer Stephen D.
JournalCell Rep
Date Published2013 Dec 26
KeywordsAnimals, Cell Line, Tumor, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Epigenetic Repression, Hematopoiesis, Humans, Methylation, Mice, MicroRNAs, Myeloid Progenitor Cells, Protein Binding, Protein-Arginine N-Methyltransferases, RNA Processing, Post-Transcriptional, Transcription Factors

<p>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 in vitro and their decreased proliferation in vivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia.</p>

Alternate JournalCell Rep
PubMed ID24332853
PubMed Central IDPMC4073674
Grant ListR01 CA166835 / CA / NCI NIH HHS / United States
R01CA166835 / CA / NCI NIH HHS / United States
U10 CA021115 / CA / NCI NIH HHS / United States
P30 CA08748 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U10 CA037403 / CA / NCI NIH HHS / United States
U24 CA114737 / CA / NCI NIH HHS / United States