Diverse DNA methylation statuses at alternative promoters of human genes in various tissues
Diverse DNA methylation statuses at alternative promoters of human genes in various tissues
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DOI：
10.1093/dnares/dsl008
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发表时间：
2006-08-31
期刊：
影响因子：
4.1
通讯作者：
Suzuki, Yutaka
中科院分区：
文献类型：
--
作者：
Cheong, Jieun;Yamada, Yoichi;Suzuki, Yutaka
我们对 5 个正常组织中 61 个人类基因的 144 个组织偏向性和 37 个非组织偏向性替代启动子的 DNA 甲基化状态进行了表征。对收集到的数据进行分析表明，（i）同一基因的不同启动子之间的 DNA 甲基化状态差异很大； (ii) 大多数个体启动子的 DNA 甲基化状态在组织之间存在差异，(iii) 在所检查的五个组织中，80-90% 的含有 CpG 岛的启动子在任一等位基因上均未甲基化。此外，虽然统计显着性不如上述特征那么明显，但我们还发现（iv）组织偏向启动子的DNA甲基化模式比非组织偏向启动子的DNA甲基化模式变化更大； (v) 组织偏向启动子在其优先表达的组织中往往比其各自的替代启动子甲基化程度较低，并且 (vi) 给定启动子的“无效”甲基化模式在转录最活跃的组织中富集。这些发现共同表明DNA甲基化存在动态的生理变化。 DNA 甲基化似乎在替代启动子的差异使用中发挥着重要作用，并且可能与含有 CpG 岛的启动子和不含 CpG 岛的启动子之间的功能多样化有关。
We characterized the DNA methylation status at 144 tissue-biased and 37 non-tissue-biased alternative promoters of 61 human genes in five normal tissues. Analysis of the collected data revealed that (i) DNA methylation status differed greatly among alternative promoters belonging to the same gene; (ii) DNA methylation status differed between tissues for the majority of the individual promoters, and (iii) 80-90% of CpG-island-containing promoters were not methylated on either allele throughout the five tissues examined. Furthermore, although the statistical significance was not as clear as for the above features, we also found that (iv) the DNA methylation patterns of tissue-biased promoters changed more drastically than those of non-tissue-biased promoters; (v) tissue-biased promoters tended to be less methylated than their respective alternative promoters in the tissues where they were preferentially expressed, and (vi) the 'null' methylation pattern of a given promoter was enriched in the tissues where the transcription was most active. These findings together indicate that there are dynamic physiological changes of DNA methylation. DNA methylation appears to play a significant role in differential usage of alternative promoters and may be related to functional diversification between CpG-island-containing promoters and CpG-island-less promoters.