Inferring causal relationships among different histone modifications and gene expression
Inferring causal relationships among different histone modifications and gene expression
复制标题
推断不同组蛋白修饰和基因表达之间的因果关系。
DOI：
10.1101/gr.073080.107
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发表时间：
2008-08-01
期刊：
影响因子：
7
通讯作者：
Han, Jing-Dong J.
中科院分区：
文献类型：
--
作者：
Yu, Hong;Zhu, Shanshan;Han, Jing-Dong J.
组蛋白修饰是调控基因表达的主要表观遗传因素。它们在维持干细胞多能性和癌症发病机制中起重要作用。不同的修饰可以结合联合收割机形成复杂的“组蛋白密码”。最近的高通量技术，如“ChIP-chip”和“ChIP-seq”，已经为人类基因组上的许多组蛋白修饰生成了高分辨率的图谱。在这里，我们使用这些地图建立贝叶斯网络来推断组蛋白修饰和基因表达之间的因果关系和组合关系。目前的文献准确地支持了在多梳组（PcG）基因和H3 K27三甲基化之间通过相同方法导出的先导网络。交叉验证结果也很好地支持了我们在组蛋白修饰之间的无偏网络模型。它不仅证实了已知的关系，如H3 K27 me 3基因沉默，H3 K4 me 3基因激活和H3 K4 me 3和H3 K27 me 3的双价修饰的效果，但也确定了许多其他关系，可能预测新的表观遗传相互作用的重要表观遗传基因调控。我们的自动推理方法，这是潜在的适用于其他ChIP-chip或ChIP-seq数据分析，提供了一个急需的指导破译复杂的组蛋白代码。
Histone modifications are major epigenetic factors regulating gene expression. They play important roles in maintaining stem cell pluripotency and in cancer pathogenesis. Different modifications may combine to form complex "histone codes." Recent high-throughput technologies, such as "ChIP-chip" and "ChIP-seq," have generated high-resolution maps for many histone modifications on the human genome. Here we use these maps to build a Bayesian network to infer causal and combinatorial relationships among histone modifications and gene expression. A pilot network derived by the same method among polycomb group (PcG) genes and H3K27 trimethylation is accurately supported by current literature. Our unbiased network model among histone modifications is also well supported by cross-validation results. It not only confirmed already known relationships, such as those of H3K27me3 to gene silencing, H3K4me3 to gene activation and the effect of bivalent modification of both H3K4me3 and H3K27me3, but also identified many other relationships that may predict new epigenetic interactions important in epigenetic gene regulation. Our automated inference method, which is potentially applicable to other ChIP-chip or ChIP-seq data analyses, provides a much-needed guide to deciphering the complex histone codes.