PRMT4 Blocks Myeloid Differentiation by Assembling a Methyl-RUNX1-Dependent Repressor Complex
Year: 2013
Type: article
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 in vitro and their decreased proliferation in vivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia.
Source: Cell Reports
Institutions: Memorial Sloan Kettering Cancer Center, University of Miami, Sylvester Comprehensive Cancer Center, University of Michigan, Michigan Medicine, Indiana University Indianapolis, Indiana University School of Medicine, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, Weill Cornell Medicine, University of Alabama, University of Alabama at Birmingham
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W2103432725