Mechanics of Transcription Regulation

转录调控机制

• 批准号: 0528296
• 负责人: Sean Sun
• 金额: $ 18.21万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-10-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0528296&HistoricalAwards=false
• 关键词: Mechanics; Transcription; Regulation

In the nucleus of animal cells, DNA is densely packed into a highly dynamic structure called the chromosome. The basic structural component of chromosomes is chromatin. Chromatin organizes DNA into tight bundles and thus achieving high density storage of genetic information. Even though the biochemistry of DNA transcription is becoming clear, the mechanics of chromatin and its influence on DNA transcription is largely unexplored. For instance, how does the transcription protein physically access the relevant regions of the DNA? Can we explain the elastic behavior of chromatin from fundamental considerations? The investigators use a multi-scale computational modeling approach to explore the mechanics of chromatin fiber. They specifically address the following questions: 1) Given the topological constraints, what are the static (equilibrium) structure of chromatin and its elastic properties? 2) What is the dynamics of chromatin formation? How is remodeling of chromatin accomplished in vivo? 3) How is chromatin remodeling responsible for modifying the mechanics of transcription, and what are the roles of gene regulatory proteins and DNA topoisomerases in initiating and modulating transcription? The answers to the questions have fundamental importance in our understanding of how genetic information is organized and transmitted in cells.

在动物细胞的核中，将DNA密集地包装成一种称为染色体的高度动态结构。染色体的基本结构成分是染色质。 染色质将DNA组织成紧密的束，从而实现了遗传信息的高密度存储。 即使DNA转录的生物化学越来越清晰，染色质的力学及其对DNA转录的影响在很大程度上尚未探索。例如，转录蛋白如何物理访问DNA的相关区域？我们可以从基本考虑上解释染色质的弹性行为吗？研究人员使用多尺度的计算建模方法来探索染色质纤维的力学。他们特别解决了以下问题：1）给定拓扑约束，染色质及其弹性特性的静态（平衡）结构是什么？ 2）染色质形成的动力学是什么？如何在体内完成染色质的重塑？ 3）染色质重塑如何负责修饰转录力学，以及基因调节蛋白和DNA拓扑异构酶在启动和调节转录中的作用是什么？问题的答案对于我们对细胞中遗传信息的组织和传播方式的理解至关重要。