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首页> 外文期刊>Genomics >Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy
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Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy

机译：甲基化分析显示人类扩张型心肌病左心室发育基因调控区域DNA甲基化的改变

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Dilated cardiomyopathy (DCM) is one of the main causes of heart failure (called cardiomyopathies) in adults. Alterations in epigenetic regulation (i.e., DNA methylation) have been implicated in the development of DCM. Here, we identified a total of 1828 differentially methylated probes (DMPs) using the Infinium 450K HumanMethylation Bead chip by comparing the methylomes between 18 left ventricles and 9 right ventricles. Alterations in DNA methylation levels were observed mainly in lowly methylated regions corresponding to promoter-proximal regions, which become hypermethylated in severely affected left ventricles. Subsequent mRNA microarray analysis showed that the effect of DNA methylation on gene expression regulation is not unidirectional but is controlled by the functional sub-network context. DMPs were significantly enriched in the transcription factor binding sites (TFBSs) we tested. Alterations in DNA methylation were specifically enriched in the cis-regulatory regions of cardiac development genes, the majority of which are involved in ventricular development (e.g., TBX5 and HAND1). (C) 2016 The Authors. Published by Elsevier Inc.
机译：扩张型心肌病（DCM）是成年人心力衰竭（称为心肌病）的主要原因之一。表观遗传调控的改变（即，DNA甲基化）已经涉及DCM的发展。在这里，我们通过比较18个左心室和9个右心室之间的甲基化组，使用Infinium 450K HumanMethylation Bead芯片鉴定出总共1828个差异甲基化探针（DMP）。 DNA甲基化水平的变化主要在对应于启动子近端区域的低甲基化区域中观察到，这些区域在严重受影响的左心室中变得高度甲基化。随后的mRNA微阵列分析表明，DNA甲基化对基因表达调控的影响不是单向的，而是受功能子网环境的控制。 DMP在我们测试的转录因子结合位点（TFBS）中明显富集。 DNA甲基化的改变特别丰富于心脏发育基因的顺式调控区域，其中大部分与心室发育有关（例如TBX5和HAND1）。 （C）2016作者。由Elsevier Inc.发布

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