基于深度测序和Hi-C方法对染色体层次上基因表达调控机制的研究

项目名称： 基于深度测序和Hi-C方法对染色体层次上基因表达调控机制的研究

项目编号： No.31471248

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 肖景发

作者单位： 中国科学院北京基因组研究所

项目金额： 80万元

中文摘要： 细胞内互作染色质组的功能研究一直是基因功能研究的重点，已有研究表明大规模染色体结构和核空间重排与控制基因表达、DNA复制和修复具有关联性。但关于原核生物染色体空间结构变化如何对基因表达进程进行调控有待于深入的理解和研究, 因此亟需发展和应用新方法揭示其调控机制。围绕上述科学问题，本项目拟以大肠杆菌作为研究对象，通过RNA-Seq方法获得大肠杆菌不同生长时期的表达谱, 界定其适应环境变化的关键调控基因，再结合Hi-C方法构建其染色体相互作用图谱, 研究在生长过程中染色体结构变化规律，并通过关联分析发现在大肠杆菌生长过程中染色体结构变化对基因表达的影响。最终目的是建立一套原核生物染色体结构捕获和转录组数据分析模型，从染色体结构层面上阐明基因表达调控机制，为全面解析原核生物基因表达调控提供新的思路。

中文关键词： 基因表达调控；Hi-C方法；染色体结构；深度测序；原核生物

英文摘要： The functional study of chromosome interactomes is the keystone of gene function research.The previous studies show that large-scale chromosome structure and nucleus space rearrangement are associated with the governing of gene expression, DNA replication and repair. But how the change of chromosome spatial structure regulates gene expression in prokaryote is still unknown. New methodology and applications need to be developed to reveal the regulatory mechanism of gene expression. This proposal will focus on the above scientific problems; choose E. coli as the investigating target; construct expression profiles of E. coli in different growth stages by RNA-Seq method; identify the key regulated genes that adapt to the environmental changes; access the chromosome interaction map by using chromosome conformation capture coupled with deep sequencing method (Hi-C); investigate the chromosome structure variation in different growth process; and find out how chromosome structure variation effects gene expression in different growth process through association analysis. The ultimate objective is to establish a model to capture the prokaryotic chromosome structure and analyze their transcriptomics data, which could elucidate the molecular mechanism of gene expression regulation on chromosome spatial structure level and provide new thought for comprehensive analysis of prokaryotic gene expression regulation.

英文关键词： regulation of gene expression;chromosome conformation capture coupled with deep sequencing;chromosome structure;deep sequencing;prokaryote