PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential Journal Article

Authors: Shia, W. J.; Okumura, A. J.; Yan, M.; Sarkeshik, A.; Lo, M. C.; Matsuura, S.; Komeno, Y.; Zhao, X.; Nimer, S. D.; Yates, J. R. 3rd; Zhang, D. E.
Article Title: PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential
Abstract: Fusion protein AML1-ETO, resulting from t(8;21) translocation, is highly related to leukemia development. It has been reported that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. We have previously shown that the expression of AE9a, a splice isoform of AML1-ETO, can rapidly cause leukemia in mice. To understand how AML1-ETO is involved in leukemia development, we took advantage of our AE9a leukemia model and sought to identify its interacting proteins from primary leukemic cells. Here, we report the discovery of a novel AE9a binding partner PRMT1 (protein arginine methyltransferase 1). PRMT1 not only interacts with but also weakly methylates arginine 142 of AE9a. Knockdown of PRMT1 affects expression of a specific group of AE9a-activated genes. We also show that AE9a recruits PRMT1 to promoters of AE9a-activated genes, resulting in enrichment of H4 arginine 3 methylation, H3 Lys9/14 acetylation, and transcription activation. More importantly, knockdown of PRMT1 suppresses the self-renewal capability of AE9a, suggesting a potential role of PRMT1 in regulating leukemia development.© 2012 by The American Society of Hematology.
Keywords: controlled study; unclassified drug; promoter region; nonhuman; protein function; cell proliferation; animal cell; animals; mice; cells, cultured; gene expression profiling; protein protein interaction; transcription initiation; protein; protein binding; cell renewal; gene expression regulation; gene activation; hybrid protein; microarray analysis; oncogene proteins, fusion; stem cells; hematopoietic stem cell; gene silencing; up-regulation; repressor proteins; transcriptional activation; lysine; arginine; protein methylation; core binding factor alpha 2 subunit; gene expression regulation, leukemic; transcription factor runx1; histone h4; protein arginine methyltransferase; k562 cells; hek293 cells; histone methylation; ae9a protein; mtg8 protein; protein arginine methyltransferase 1; protein-arginine n-methyltransferases
Journal Title: Blood
Volume: 119
Issue: 21
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2012-05-24
Start Page: 4953
End Page: 4962
Language: English
DOI: 10.1182/blood-2011-04-347476
PROVIDER: scopus
PMCID: PMC3367897
PUBMED: 22498736
Notes: --- - "Export Date: 2 July 2012" - "CODEN: BLOOA" - "Source: Scopus"
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MSK Authors
  1. Stephen D Nimer
    345 Nimer
  2. Xinyang Zhao
    29 Zhao