N6-Methyldeoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation

Marie Pierre Charles, Jean Luc Ravanat, Danièle Adamski, Gabriella D'Orazi, Jean Cadet, Alain Favier, François Berger, Didier Wion

Research output: Contribution to journalArticle

Abstract

N6-methyl-2′-deoxyadenosine (MedAdo) is a nucleoside naturally found in prokaryotic DNA. Interestingly, the N6- methylation of adenine in DNA seems to have been counter-selected during the course of evolution since MedAdo has not been detected in mammalian DNA until now. We show here that treatment with MedAdo induces myogenesis in C2C12 myoblasts. The presence of MedAdo in C2C12 DNA was investigated using a method based on HPLC coupled to electrospray ionization tandem mass spectrometry which is several thousand fold more sensitive than assays used previously. By this procedure, MedAdo is detected in the DNA from MedAdo-treated cells but remains undetectable in the DNA from control cells. Furthermore, MedAdo regulates the expression of p21, myogenin, mTOR, and MHC. Interestingly, in the pluripotent C2C12 cell line, MedAdo drives the differentiation towards myogenesis only. Thus, the biological effect of MedAdo is suppressed in the presence of BMP-2 which transdifferentiates C2C12 from myogenic into osteogenic lineage cells. Taken together these results point to MedAdo as a novel inducer of myogenesis and further extends the differentiation potentialities of this methylated nucleoside. Furthermore, these data raise the intriguing possibility that the biological effects of MedAdo on cell differentiation may have led to its counter-selection in eukaryotes.

Original languageEnglish
Pages (from-to)476-482
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number2
DOIs
Publication statusPublished - Feb 6 2004

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Keywords

  • C2C12
  • Cell differentiation
  • Myogenesis
  • N-Methyl-2′-deoxyadenosine

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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