title: Epigenetic regulation of neonatal cardiomyocytes differentiation.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Cecy Ying-Chuck
authors.initials: CY
authors.lastname: Kou
authors.forename: Samantha Lai-Yee
authors.initials: SL
authors.lastname: Lau
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Au
authors.forename: Pui-Yin
authors.initials: PY
authors.lastname: Leung
authors.forename: Stephen Siu-Chung
authors.initials: SS
authors.lastname: Chim
authors.forename: Kwok-Pui
authors.initials: KP
authors.lastname: Fung
authors.forename: Mary Miu-Yee
authors.initials: MM
authors.lastname: Waye
authors.forename: Stephen Kwok-Wing
authors.initials: SK
authors.lastname: Tsui
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D015257:DNA-Cytosine Methylases / Q000235:genetics; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D015257:DNA-Cytosine Methylases; D001374:Azacitidine