人类疾病中非编码 RNA 的异常表观遗传修饰。
Aberrant Epigenetic Modifications of Non-coding RNAs in Human Disease.
机构信息
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
出版信息
Adv Exp Med Biol. 2018;1094:65-75. doi: 10.1007/978-981-13-0719-5_7.
Non-coding RNAs, especially lncRNAs, have emerged as key components in histone modification. The alterations in the epigenetic modifications of lncRNAs underlie some human disorders ranging from neurodegeneration to cancer. To characterize the epigenetic modifications of lncRNAs, we first constructed the histone modification maps of various epigenetic markers across different cell lines. Then, we developed a method to identify epigenetically regulated lncRNAs and their response genes by integrating large scale epigenetic and transcriptional profiles. Our results showed that epigenetic alterations at the promoters of lncRNAs can influence their expression and the negative response genes of most epigenetically regulated lncRNAs were enriched for PRC2-binding genes. At last, we inferred some lncRNAs with aberrant epigenetic modifications in glioblastoma and Alzheimer's disease, and proved that theses lncRNAs may contribute to the initiation of human diseases.
非编码 RNA，尤其是长链非编码 RNA，已成为组蛋白修饰的关键成分。lncRNA 的表观遗传修饰的改变是从神经退行性疾病到癌症等多种人类疾病的基础。为了描述 lncRNA 的表观遗传修饰，我们首先构建了不同细胞系中各种表观遗传标记的组蛋白修饰图谱。然后，我们开发了一种方法，通过整合大规模的表观遗传和转录组数据来鉴定受表观遗传调控的 lncRNA 及其反应基因。我们的结果表明，lncRNA 启动子上的表观遗传改变可以影响它们的表达，并且大多数受表观遗传调控的 lncRNA 的负反应基因富集了 PRC2 结合基因。最后，我们推断出胶质母细胞瘤和阿尔茨海默病中存在异常的表观遗传修饰的一些 lncRNA，并证明这些 lncRNA 可能有助于人类疾病的发生。
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