A human B cell methylome at 100-base pair resolution
A human B cell methylome at 100-base pair resolution
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DOI：
10.1073/pnas.0812399106
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发表时间：
2009-01-20
影响因子：
11.1
通讯作者：
Pfeifer, Gerd P.
中科院分区：
文献类型：
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作者：
Rauch, Tibor A.;Wu, Xiwei;Pfeifer, Gerd P.
使用甲基化DNA富集技术（甲基化CpG岛恢复测定，MIRA）结合全基因组平铺阵列，我们通过MIRA芯片以100 bp分辨率表征了个体人类的整个B细胞“甲基化组”。我们发现，在染色体水平上，高CpG甲基化密度与亚端粒区域和Giemsa光带（R带）相关。在平铺阵列上可以识别的大多数最高度甲基化的区域与基因相关。发现B细胞中大约10%的启动子被甲基化，并且这种甲基化与低基因表达相关。值得注意的是，这种相关性的明显例外是来自先前未鉴定的未甲基化的转录起始位点的转录的结果，这表明甲基化可能控制替代启动子的使用。发现基因内（基因体）序列的甲基化与转录的增加而非减少相关，并且在所有基因的约12%中发现了3'端附近的甲基化区域。大部分宽区域（10-44 kb）的高甲基化是在节段性重复。我们的数据为分析分化的人类细胞类型中的CpG甲基化模式提供了有价值的资源，并为哺乳动物DNA甲基化的功能提供了新的线索。
Using a methylated-DNA enrichment technique (methylated CpG island recovery assay, MIRA) in combination with whole-genome tiling arrays, we have characterized by MIRA-chip the entire B cell "methylome'' of an individual human at 100-bp resolution. We find that at the chromosome level high CpG methylation density is correlated with subtelomeric regions and Giemsa-light bands (R bands). The majority of the most highly methylated regions that could be identified on the tiling arrays were associated with genes. Approximately 10% of all promoters in B cells were found to be methylated, and this methylation correlates with low gene expression. Notably, apparent exceptions to this correlation were the result of transcription from previously unidentified, unmethylated transcription start sites, suggesting that methylation may control alternate promoter usage. Methylation of intragenic (gene body) sequences was found to correlate with increased, not decreased, transcription, and a methylated region near the 3' end was found in approximately 12% of all genes. The majority of broad regions (10-44 kb) of high methylation were at segmental duplications. Our data provide a valuable resource for the analysis of CpG methylation patterns in a differentiated human cell type and provide new clues regarding the function of mammalian DNA methylation.