Epigenetic regulation of neonatal cardiomyocytes differentiation
Epigenetic regulation of neonatal cardiomyocytes differentiation
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DOI：
10.1016/j.bbrc.2010.08.064
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发表时间：
2010-09-17
影响因子：
3.1
通讯作者：
Tsui, Stephen Kwok-Wing
中科院分区：
文献类型：
--
作者：
Kou, Cecy Ying-Chuck;Lau, Samantha Lai-Yee;Tsui, Stephen Kwok-Wing
本研究探讨心肌细胞DNA甲基化、组蛋白修饰与终末分化的关系。在新生大鼠心脏发育过程中，观察到甲基化相关蛋白的上调，包括DNA甲基转移酶（DNMT）1，甲基-CpG结合结构域蛋白1，2和3，以及整体甲基化的增加。此外，在5-氮胞苷（5-azaC）处理的心肌细胞中发现DNA合成增加和分化延迟。H3-K9、H4-K5、H4-K8的乙酰化和H3-K4的甲基化的增加表明在5-azaC处理的细胞中更易接近的染色质结构。此外，甲基-CpG结合蛋白2被发现在分化的心肌细胞中上调。该蛋白的过表达导致整体甲基化水平的增加。因此，我们认为在心肌细胞终末分化过程中形成了高甲基化的基因组和更紧凑的染色质结构。(C)2010年爱思唯尔公司All rights reserved.
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. (C) 2010 Elsevier Inc. All rights reserved.