Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region: A priming effect on the spreading of active demethylation?

Andrea Fuso, Giampiero Ferraguti, Francesco Grandoni, Raffaella Ruggeri, Sigfrido Scarpa, Roberto Strom, Marco Lucarelli

Research output: Contribution to journalArticlepeer-review

Abstract

The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5́-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation, with an active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region.

Original languageEnglish
Pages (from-to)3965-3976
Number of pages12
JournalCell Cycle
Volume9
Issue number19
DOIs
Publication statusPublished - Oct 1 2010

Keywords

  • Active demethylation
  • Demethylation dynamics
  • Muscle differentiation
  • Non-CpG island genes
  • non-CpG methylation
  • Short CpC-rich elements
  • Transcriptional modulation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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