提供大家看篇表观遗传和miRNA,血管新生的文章

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Epigenetic mechanisms such as microRNA and histone modification are crucially responsible for dysregulated gene expression in heart failure. In contrast, the role of DNA methylation, another well-characterized epigenetic mark, is unknown. In order to examine whether human cardiomyopathy of different etiologies are connected by a unifying pattern of DNA methylation pattern, we undertook profiling with ischaemic and idiopathic end-stage cardiomyopathic left ventricular (LV) explants from patients who had undergone cardiac transplantation compared to normal control. We performed a preliminary analysis using methylated-DNA immunoprecipitation-chip (MeDIP-chip), validated differential methylation loci by bisulfite-(BS) PCR and high throughput sequencing, and identified 3 angiogenesis-related genetic loci that were differentially methylated. Using quantitative RT-PCR, we found that the expression of these genes differed significantly between CM hearts and normal control (p,0.01). Moreover, for each individual LV tissue, differential methylation showed a predicted correlation to differential expression of the corresponding gene. Thus, differential DNA methylation exists in human cardiomyopathy. In this series of heterogenous cardiomyopathic LV explants, differential DNA methylation was found in at least 3 angiogenesis-related genes. While in other systems, changes in DNA methylation at specific genomic loci usually precede changes in the expression of corresponding genes, our current findings in cardiomyopathy merit further investigation to determine whether DNA methylation changes play a causative role in the progression of heart failure.& W5 `! x, j. z& I( j
研究证明在心衰方面表观遗传机制（如miRNA和组蛋白修饰）起着调节基因表达的重要作用。然而，DNA甲基化（另一个表观遗传标志）的作用却不清楚。为了验证不同病因的心肌病是否有着同一套DNA甲基化模式，我们研究了因车祸死亡的并发缺血损伤或晚期先天性心机病的病人的心脏左室LV组织。我们采用DNA甲基化免疫沉淀芯片技术、BS-PCR和高通量测序技术验证了3个血管生成相关基因位点发生了特异甲基化现象。还利用q-PCR发现CM心脏中这几个基因表达量明显与对照组不同。再有，对于每份LV组织甲基化现象都与其相关基因有着特异相关性。所以，DNA特异甲基化是存在于人类心肌病组织中的。在这一系列的不同的LV组织中发现至少有3个血管生成相关基因与DNA甲基化有关。同时，特异基因位点上发生DNA甲基化，通常预示着相关基因也会改变，我们现阶段的发现是为了进一步探明DNA甲基化在心衰研究方面的作用。

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safflower

DNA特异甲基化在多种疾病的发生中起着很重要的作用，不知发现的这3个血管生成相关基因是否是关键基因？