Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation
Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation
复制标题
通过表观基因组操作揭示启动子 DNA 甲基化的全基因组抑制能力
DOI：
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复制
发表时间：
2018
期刊：
影响因子：
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通讯作者：
R. Irizarry
中科院分区：
文献类型：
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作者：
Keegan D. Korthauer;R. Irizarry
科学界越来越多地接受开放科学。这种对开放科学日益增长的承诺应该受到赞扬和鼓励，特别是在自愿和同行评议之前。感谢其他研究人员对开放科学的奉献，我们有幸对一个具有里程碑意义的实验进行了重新分析，该实验以预印本的形式发表，并在公共存储库中提供了数据。该研究发现，启动子DNA甲基化通常不足以诱导转录抑制，这似乎与大量观察性研究相矛盾，这些研究表明DNA甲基化与基因表达之间存在强烈关联。这项研究首次评估了强制甲基化数千个DNA启动子区域是否足以抑制基因表达。作者的数据分析没有发现启动子甲基化和转录抑制之间有很强的关系。然而，他们的分析没有充分利用统计推断，而是应用了一种归一化技术，消除了代表实际生物系统的全局差异。在这里，我们重新分析数据的方法，包括差异甲基化区域的统计推断，以及一个标准化技术，占全球表达差异。我们发现，成千上万的启动子的强制DNA甲基化压倒性地抑制基因表达。此外，我们发现，作为DNA甲基化的结果，活性转录的互补表观遗传标记减少。最后，通过研究这些协会是否是敏感的CG密度的启动子，我们发现没有实质性的差异，启动子之间的关联与CG岛。复制分析所需的代码包含在公共GitHub存储库github.com/kdkorthauer/repressivecapacity中。
The scientific community is increasingly embracing open science. This growing commitment to open science should be applauded and encouraged, especially when it occurs voluntarily and prior to peer review. Thanks to other researchers’ dedication to open science, we have had the privilege of conducting a reanalysis of a landmark experiment published as a preprint with data made available in a public repository. The study in question found that promoter DNA methylation is frequently insufficient to induce transcriptional repression, which appears to contradict a large body of observational studies showing a strong association between DNA methylation and gene expression. This study was the first to evaluate whether forcibly methylating thousands of DNA promoter regions is sufficient to suppress gene expression. The authors’ data analysis did not find a strong relationship between promoter methylation and transcriptional repression. However, their analyses did not make full use of statistical inference and applied a normalization technique that removes global differences that are representative of the actual biological system. Here we reanalyze the data with an approach that includes statistical inference of differentially methylated regions, as well as a normalization technique that accounts for global expression differences. We find that forced DNA methylation of thousands of promoters overwhelmingly represses gene expression. In addition, we show that complementary epigenetic marks of active transcription are reduced as a result of DNA methylation. Finally, by studying whether these associations are sensitive to the CG density of promoters, we find no substantial differences in the association between promoters with and without a CG island. The code needed to reproduce are analysis is included in the public GitHub repository github.com/kdkorthauer/repressivecapacity.
影响因子：
16
作者：
Goentoro L;Kirschner MW
通讯作者：
Kirschner MW