Epigenetic regulation of neonatal cardiomyocytes differentiation.
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.
Kou
Cecy Ying-Chuck
CY
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong.
Lau
Samantha Lai-Yee
SL
Au
Ka-Wing
KW
Leung
Pui-Yin
PY
Chim
Stephen Siu-Chung
SS
Fung
Kwok-Pui
KP
Waye
Mary Miu-Yee
MM
Tsui
Stephen Kwok-Wing
SK
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
D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D015257:DNA-Cytosine Methylases; D001374:Azacitidine