生物谷報(bào)道:組蛋白修飾是調(diào)控基因表達(dá)的重要表觀遺傳學(xué)機(jī)制,,在保持胚胎干細(xì)胞的全能性以及癌癥的病理過程中起到了重要的作用。不同的組蛋白修飾有可能組成復(fù)雜的“組蛋白編碼”,。
近兩年來,高通量的染色體免疫沉淀結(jié)合全基因組DNA芯片或新一代短序列測序技術(shù)(“ChIP-chip”和“ChIP-seq”)產(chǎn)生了高清晰度的人類全基因組上的諸多組蛋白修飾位點(diǎn),。中科院韓敬東研究組在此基礎(chǔ)上,利用貝葉斯網(wǎng)絡(luò)推測組蛋白各種不同修飾和基因表達(dá)之間的因果關(guān)系及組合關(guān)系,。該方法在PcG復(fù)合物和H3K27me3的數(shù)據(jù)上進(jìn)行測試,,所得結(jié)論和現(xiàn)有的實(shí)驗(yàn)結(jié)果一致。組蛋白各種不同修飾和基因表達(dá)之間建立的貝葉斯網(wǎng)絡(luò)具有很好的交叉驗(yàn)證結(jié)果,。它不僅吻合很多已知的組蛋白與基因表達(dá)的關(guān)系(如H3K27me3抑制基因表達(dá),,H3K4me3促進(jìn)基因表達(dá),以及這兩種修飾的共同影響),,而且發(fā)現(xiàn)了許多新的組蛋白修飾和基因表達(dá)之間的關(guān)系,,以及組蛋白修飾相互之間形成的邏輯關(guān)系。
該工作為人們認(rèn)識(shí)不同組蛋白修飾之間的復(fù)雜關(guān)系及其對(duì)基因表達(dá)的影響提供了一個(gè)新的視角,,同時(shí)也為該領(lǐng)域提供了一種十分重要的研究方法,,是破譯復(fù)雜的“組蛋白編碼”研究方面的重要進(jìn)展。該結(jié)果已經(jīng)發(fā)表在6月18日的《基因組研究》(Genome Research)上,。(生物谷www.bioon.com)
生物谷推薦原始出處:
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.