Mechanism of Bacterial Enhancer-Dependent Transcription

细菌增强子依赖性转录机制

• 批准号: 0549593
• 负责人: Vasily Studitsky
• 金额: --
• 依托单位: Rutgers, The State University of New Jersey-RBHS-Robert Wood
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-15 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0549593&HistoricalAwards=false
• 关键词: Mechanism; Bacterial; Enhancer; Dependent; Transcription

Transcription (the first step in gene expression) is essential for all living organisms. On the majority of genes transcription is regulated by enhancers - DNA sequences regulating transcription over a distance. The goal of this project is to understand the mechanism of transcription regulation by enhancers, including action over a large distance. The primary features of this process have been recapitulated in vitro in a highly purified bacterial system. Enhancer action involves direct interaction between the proteins bound at the enhancer sites and their targets (promoters) with accompanying looping of the spacer DNA. Recently it has been shown that the action of enhancers requires: (1) unique tertiary DNA structure that can greatly facilitate enhancer-promoter communication and (2) unique structure of the enhancer targets. This project focuses on further analysis of these two crucial aspects of the mechanism of enhancer action and transcription regulation. The mechanism of enhancer action will be analyzed using biochemical and molecular genetic approaches. New techniques and strategies for the analysis of protein-DNA and protein-protein interactions, including interactions over a distance will be developed. Completion of this project will result in better understanding of the mechanism of transcription regulation over a distance. The results obtained will also have direct implications for understanding of other processes regulated over a distance (such as DNA replication, recombination and repair) and will be broadly applicable to both prokaryotic and eukaryotic systems. The project will train undergraduate and graduate students in biochemistry and molecular biology.

转录（基因表达的第一步）对所有生物体都是必不可少的。在大多数基因上，转录是由增强子调节的- DNA序列在一定距离上调节转录。该项目的目标是了解增强子的转录调节机制，包括大距离作用。该过程的主要特征已在体外高度纯化的细菌系统中重现。增强子作用涉及在增强子位点结合的蛋白质与它们的靶（启动子）之间的直接相互作用，伴随着间隔区DNA的成环。最近已经表明，增强子的作用需要：（1）可以极大地促进增强子-启动子通信的独特的三级DNA结构和（2）增强子靶标的独特结构。本项目的重点是进一步分析增强子作用和转录调控机制的这两个关键方面。增强子作用的机制将使用生物化学和分子遗传学方法进行分析。将开发分析蛋白质-DNA和蛋白质-蛋白质相互作用（包括远距离相互作用）的新技术和策略。这个项目的完成将导致更好地理解转录调控的机制。所获得的结果也将有直接的影响，了解其他过程的调控距离（如DNA复制，重组和修复），并将广泛适用于原核和真核系统。该项目将培养生物化学和分子生物学的本科生和研究生。