生物谷报道:组蛋白修饰是调控基因表达的重要表观遗传学机制,在保持胚胎干细胞的全能性以及癌症的病理过程中起到了重要的作用。不同的组蛋白修饰有可能组成复杂的“组蛋白编码”。
近两年来,高通量的染色体免疫沉淀结合全基因组DNA芯片或新一代短序列测序技术(“ChIP-chip”和“ChIP-seq”)产生了高清晰度的人类全基因组上的诸多组蛋白修饰位点。中科院韩敬东研究组在此基础上,利用贝叶斯网络推测组蛋白各种不同修饰和基因表达之间的因果关系及组合关系。该方法在PcG复合物和H3K27me3的数据上进行测试,所得结论和现有的实验结果一致。组蛋白各种不同修饰和基因表达之间建立的贝叶斯网络具有很好的交叉验证结果。它不仅吻合很多已知的组蛋白与基因表达的关系(如H3K27me3抑制基因表达,H3K4me3促进基因表达,以及这两种修饰的共同影响),而且发现了许多新的组蛋白修饰和基因表达之间的关系,以及组蛋白修饰相互之间形成的逻辑关系。
该工作为人们认识不同组蛋白修饰之间的复杂关系及其对基因表达的影响提供了一个新的视角,同时也为该领域提供了一种十分重要的研究方法,是破译复杂的“组蛋白编码”研究方面的重要进展。该结果已经发表在6月18日的《基因组研究》(Genome Research)上。(生物谷www.bioon.com)
生物谷推荐原始出处:
Genome Research,10.1101/gr.073080.107,Hong Yu, Jing-Dong Jackie Han
Inferring causal relationships among different histone modifications and gene expression
Hong Yu, Shanshan Zhu, Bing Zhou, Huiling Xue, and Jing-Dong Jackie Han1
Chinese Academy of Sciences
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.