PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma

Nat Commun. 2018 Oct 31;9(1):4552. doi: 10.1038/s41467-018-06968-7.


Transcriptional deregulation has a vital role in glioblastoma multiforme (GBM). Thus, identification of epigenetic modifiers essential for oncogenic transcriptional programs is a key to designing effective therapeutics for this deadly disease. Here we report that Protein Arginine Methyltransferase 2 (PRMT2) is highly expressed in GBM and correlated with poor prognosis. The silencing or inactivation of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro, and suppresses orthotopic tumor growth, accompanied with significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. Mechanistically PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a), whose enrichment at promoters and enhancers is closely correlated with known active histone marks and is required for the maintenance of target gene expression. Together, this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Self Renewal
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Histones / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Methylation
  • Oncogenes*
  • Promoter Regions, Genetic / genetics
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Transcription, Genetic


  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Arginine
  • PRMT2 protein, human
  • Protein-Arginine N-Methyltransferases