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首页> 外文期刊>Epigenetics & Chromatin >Tissue-specific variation in DNA methylation levels along human chromosome 1
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Tissue-specific variation in DNA methylation levels along human chromosome 1

机译：沿人类1号染色体的DNA甲基化水平的组织特异性变异

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Background DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Most methods to scan the genome in different tissues for differentially methylated sites have focused on the methylation of CpGs in CpG islands, which are concentrations of CpGs often associated with gene promoters. Results Here, we use a methylation profiling strategy that is predominantly responsive to methylation differences outside of CpG islands. The method compares the yield from two samples of size-selected fragments generated by a methylation-sensitive restriction enzyme. We then profile nine different normal tissues from two human donors relative to spleen using a custom array of genomic clones covering the euchromatic portion of human chromosome 1 and representing 8% of the human genome. We observe gross regional differences in methylation states across chromosome 1 between tissues from the same individual, with the most striking differences detected in the comparison of cerebellum and spleen. Profiles of the same tissue from different donors are strikingly similar, as are the profiles of different lobes of the brain. Comparing our results with published gene expression levels, we find that clones exhibiting extreme ratios reflecting low relative methylation are statistically enriched for genes with high expression ratios, and vice versa, in most pairs of tissues examined. Conclusion The varied patterns of methylation differences detected between tissues by our methylation profiling method reinforce the potential functional significance of regional differences in methylation levels outside of CpG islands.
机译：背景DNA甲基化是主要的表观遗传修饰，对调节基因表达和抑制假转录非常重要。扫描不同组织中基因组差异甲基化位点的大多数方法都集中于CpG岛中CpG的甲基化，CpG岛是通常与基因启动子相关的CpG浓度。结果在这里，我们使用一种甲基化分析策略，该策略主要响应CpG岛以外的甲基化差异。该方法比较了由甲基化敏感性限制酶产生的两个大小选择的片段样品的产率。然后，我们使用覆盖人类染色体1的常染色体部分并代表人类基因组8％的基因组克隆的定制阵列，从两个人类供体相对于脾脏分析了九种不同的正常组织。我们观察到同一个人的组织之间在1号染色体上甲基化状态的总体区域差异，在比较小脑和脾脏时发现了最明显的差异。来自不同供体的同一组织的轮廓与大脑不同叶的轮廓非常相似。将我们的结果与已发表的基因表达水平进行比较，我们发现在大多数被检查的组织中，具有高表达率的基因在统计学上富集了表现出极低比率反映低相对甲基化的克隆，反之亦然。结论我们的甲基化谱分析方法在组织之间检测到的甲基化差异的不同模式增强了CpG岛以外甲基化水平区域差异的潜在功能重要性。

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