Davuluri Ramana V
OSU Comprehensive Cancer Center, Ohio State University, Columbus, USA.
Methods Mol Biol. 2007;408:129-51. doi: 10.1007/978-1-59745-547-3_8.
The combinatorial control of gene regulatory switches involves both transcription factor (TF) complexes and associated epigenetic modifications to the chromatin template. The novel high-throughput technologies, such as Chromatin ImmunoPrecipitation ChIP-chip, have enabled genome-wide in vivo identification of TF target regulatory regions and related epigenetic modifications, which led to the view of highly dynamic TF-DNA interactions in activated or repressed promoters. Consequently, modeling and elucidating the combinatorial interaction of TFs and corresponding cis-regulatory modules in target promoters is of paramount interest. An estimated 5% of the genes in mammalian genomes code for TF proteins, and computational modeling of cis-regulatory logic would rapidly increase the pace of experimental confirmation of TF target promoters at the bench. The purpose of this chapter is to discuss the use of different bioinformatics tools for predicting the target genes of TFs of interest in mammalian genomes, and the application of these methods in the analysis of ChIP-chip experimental data. The author describes most commonly used databases and prediction programs that are available on the World Wide Web and demonstrate the use of some of these programs by an example. A list of these programs is provided along with their web Uniform Resource Locator (URLs) and guidelines for successful application are suggested.
基因调控开关的组合控制涉及转录因子(TF)复合物以及对染色质模板的相关表观遗传修饰。诸如染色质免疫沉淀芯片(Chromatin ImmunoPrecipitation ChIP-chip)等新型高通量技术,已能够在全基因组范围内对TF靶标调控区域及相关表观遗传修饰进行体内鉴定,这使得人们认识到在激活或抑制的启动子中存在高度动态的TF-DNA相互作用。因此,对靶标启动子中TF与相应顺式调控模块的组合相互作用进行建模和阐释至关重要。据估计,哺乳动物基因组中5%的基因编码TF蛋白,顺式调控逻辑的计算建模将迅速加快对TF靶标启动子进行实验验证的步伐。本章的目的是讨论如何使用不同的生物信息学工具来预测哺乳动物基因组中感兴趣的TF的靶标基因,以及这些方法在ChIP-chip实验数据分析中的应用。作者描述了万维网上最常用的数据库和预测程序,并通过一个例子展示了其中一些程序的使用方法。文中提供了这些程序的列表及其网络统一资源定位器(URL),并给出了成功应用的指导原则。