A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
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DOI：
10.3389/fgene.2012.00012
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发表时间：
2012
影响因子：
3.7
通讯作者：
Philibert RA
中科院分区：
文献类型：
--
作者：
Plume JM;Beach SR;Brody GH;Philibert RA
外周血单核细胞制剂通常用作研究人类疾病中基因表达和甲基化作用的其他组织的替代物。外周DNA甲基化的变化是否与外周血或脑基因表达的变化相关尚不清楚。为了检验前一种假设并确定哪种全基因组甲基化平台最适合我们的外周血细胞研究，我们比较了两种市售全基因组甲基化阵列的结果，这些结果与使用来自8个个体的淋巴母细胞DNA和RNA在5619个基因的启动子处的全基因组基因表达有关。我们发现，这些基因启动子的甲基化特征在不同平台之间以及与全基因组基因表达之间存在显著相关性，但这种关系的程度取决于平台的选择和甲基化程度。与其他研究的数据相结合，这些数据表明外周血细胞甲基化与基因表达相关，进一步研究以澄清这种关系的程度，以及中央和外周DNA甲基化之间的关系。
Peripheral mononuclear cell preparations are commonly used as proxies for other tissues in studies of the role of gene expression and methylation in human disease. Whether changes in peripheral DNA methylation are associated with changes in peripheral blood or brain gene expression is not clear. In order to test the former hypothesis and determine which genome-wide methylation platform was most suitable for our studies of peripheral blood cells, we compared the results from two commercially available genome-wide methylation arrays with respect to genome-wide gene expression using lymphoblast DNA and RNA from eight individuals at the promoters of 5619 genes. We found that methylation signatures at these gene promoters were significantly correlated with one another across platforms and with genome-wide gene expression, but the extent of that relationship is dependent on choice of platform and degree of methylation. Taken in context with data from other studies, these data demonstrate that peripheral blood cell methylation is associated with gene expression and that further studies to clarify the extent of this relationship, and the relationship between central and peripheral DNA methylation are in order.