Global, comparative analysis of tissue-specific promoter CpG methylation
Global, comparative analysis of tissue-specific promoter CpG methylation
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DOI：
10.1016/j.ygeno.2007.04.011
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发表时间：
2007-09-01
期刊：
影响因子：
4.4
通讯作者：
Rehli, Michael
中科院分区：
文献类型：
--
作者：
Schilling, Elinar;Rehli, Michael
在人类基因组测序完成后，在全球范围内了解细胞类型特异性表观遗传密码是一个重大挑战。在这里，我们应用甲基-CpG免疫沉淀（MCIP），以获得比较的甲基化谱的编码和非编码基因在三个人体组织，睾丸，大脑和单核细胞。44个主要是睾丸特异性启动子进行了独立验证，使用亚硫酸氢盐测序或单基因MCIP，确认MCIP微阵列方法获得的结果。我们证明了以前未知的体细胞高甲基化在许多CpG丰富，睾丸特异性基因启动子，特别是在扩增区域的Y染色体。我们还鉴定了一些显示组织特异性甲基化模式的miRNA基因。获得的组织甲基化谱与相应的基因表达数据的比较表明，组织特异性启动子甲基化和基因表达之间的显着关联，不仅在富含CpG的启动子。总之，我们的研究突出了睾丸生殖系细胞的特殊表观遗传状态，并提供了对组织特异性DNA甲基化模式的全面了解。(c)2007年爱思唯尔公司All rights reserved.
Understanding cell-type-specific epigenetic codes on a global level is a major challenge after the sequencing of the human genome has been completed. Here we applied methyl-CpG immunoprecipitation (MCIp) to obtain comparative methylation profiles of coding and noncoding genes in three human tissues, testis, brain, and monocytes. Forty-four mainly testis-specific promoters were independently validated using bisulfite sequencing or single-gene MCIp, confirming the results obtained by the MCIp microarray approach. We demonstrate the previously unknown somatic hypermethylation at many CpG-rich, testis-specific gene promoters, in particular in ampliconic areas of the Y chromosome. We also identify a number of miRNA genes showing tissue-specific methylation patterns. The comparison of the obtained tissue methylation profiles with corresponding gene expression data indicates a significant association between tissue-specific promoter methylation and gene expression, not only in CpG-rich promoters. In summary, our study highlights the exceptional epigenetic status of germ-line cells in testis and provides a global insight into tissue-specific DNA methylation patterns. (c) 2007 Elsevier Inc. All rights reserved.