The Dynamics of Myogenin Site-specific Demethylation is Strongly Correlated with its Expression and with Muscle Differentiation

Marco Lucarelli, Andrea Fuso, Roberto Strom, Sigfrido Scarpa

Research output: Contribution to journalArticlepeer-review

Abstract

The molecular mechanisms underlying the activation of tissue-specific genes have not yet been fully clarified. We analyzed the methylation status of specific CCGG sites in the 5′-flanking region and exon I of myogenin gene, a very important myogenic differentiation factor. We demonstrated a loss of methylation, at the onset of C2C12 muscle cell line differentiation, limited to the CCGG site of myogenin 5′-flanking region, which was strongly correlated with the transcriptional activation of this gene and with myogenic differentiation. The same CCGG site was also found to be hypomethylated, in vivo, in embryonic mouse muscle (a myogenin-expressing tissue), as opposed to nonmuscle (nonexpressing) tissues that had a fully methylated site. In a C2C12-derived clone with enhanced myogenic ability, demethylation occurred within 2 h of induction of differentiation, suggesting the involvement of some active demethylation mechanism(s) that occur in the absence of DNA replication. Exposure to drugs that inhibit DNA methylation by acting on the S-adenosylmethionine metabolism produced a further reduction, to a few minutes, in the duration of the demethylation dynamics. These effects suggest that the final site-specific DNA methylation pattern of tissue-specific genes is defined through a continuous, relatively fast interplay between active DNA demethylation and re-methylation mechanisms.

Original languageEnglish
Pages (from-to)7500-7506
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number10
DOIs
Publication statusPublished - Mar 9 2001

ASJC Scopus subject areas

  • Biochemistry

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