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 journalArticle

40 Citations (Scopus)

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

Fingerprint

Myogenin
5' Flanking Region
Methylation
CpG Islands
DNA Methylation
Genes
Muscles
Myoblasts
Muscle Cells
Transcriptional Activation
Transcription Factors
cytidylyl-(3'-5')-cytidine
DNA
Brain

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

Cite this

Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region : A priming effect on the spreading of active demethylation? / Fuso, Andrea; Ferraguti, Giampiero; Grandoni, Francesco; Ruggeri, Raffaella; Scarpa, Sigfrido; Strom, Roberto; Lucarelli, Marco.

In: Cell Cycle, Vol. 9, No. 19, 01.10.2010, p. 3965-3976.

Research output: Contribution to journalArticle

Fuso, Andrea ; Ferraguti, Giampiero ; Grandoni, Francesco ; Ruggeri, Raffaella ; Scarpa, Sigfrido ; Strom, Roberto ; Lucarelli, Marco. / Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region : A priming effect on the spreading of active demethylation?. In: Cell Cycle. 2010 ; Vol. 9, No. 19. pp. 3965-3976.
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