School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong.
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.
本研究探讨了 DNA 甲基化、组蛋白修饰与心肌细胞终末分化的关系。在大鼠新生心脏发育过程中观察到甲基化相关蛋白（包括 DNA 甲基转移酶 1、甲基-CpG 结合域蛋白 1、2 和 3）的上调以及整体甲基化水平的增加。此外，在 5-氮杂胞苷（5-azaC）处理的心肌细胞中发现 DNA 合成增加和分化延迟。5-azaC 处理细胞中 H3-K9、H4-K5、H4-K8 的乙酰化增加和 H3-K4 的甲基化表明染色质结构更加开放。此外，在分化的心肌细胞中发现甲基-CpG 结合蛋白 2 上调。该蛋白的过表达导致整体甲基化水平增加。因此，我们认为在心肌细胞的终末分化过程中形成了超甲基化的基因组和更紧密的染色质结构。
