Epigenetic regulation of neonatal cardiomyocytes differentiation

Biochem Biophys Res Commun. 2010 Sep 17;400(2):278-83. doi: 10.1016/j.bbrc.2010.08.064. Epub 2010 Aug 22.


The relationship between DNA methylation, histone modifications and terminal differentiation in cardiomyocytes was investigated in this study. The upregulation of methylation-related proteins, including DNA methyltransferase (DNMT) 1, methyl-CpG binding domain proteins 1, 2 and 3, and the increase in global methylation during rat neonatal heart development were observed. Moreover, an increase in DNA synthesis and a delay in differentiation were found in 5-azacytidine (5-azaC)-treated cardiomyocytes. Increase in acetylation of H3-K9, H4-K5, H4-K8 and methylation of H3-K4 suggested a more accessible chromatin structure in 5-azaC-treated cells. Furthermore, methyl-CpG-binding protein 2 was found to be upregulated in differentiated cardiomyocytes. Overexpression of this protein resulted in an increase of global methylation levels. Therefore, we suggest that a hypermethylated genome and a more compact chromatin structure are formed during terminal differentiation of cardiomyocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azacitidine / pharmacology
  • Cell Differentiation / genetics*
  • DNA Methylation / genetics*
  • DNA-Cytosine Methylases / genetics
  • Epigenesis, Genetic*
  • Histones / metabolism
  • Methyl-CpG-Binding Protein 2 / genetics
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Rats
  • Rats, Sprague-Dawley


  • Histones
  • Methyl-CpG-Binding Protein 2
  • DNA-Cytosine Methylases
  • Azacitidine