Evolutionary Mechanisms Governing Gene Regulation

基因调控的进化机制

• 批准号: 6853590
• 负责人: Martin E KREITMAN
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853590
• 关键词: Drosophilidae; arthropod genetics; binding sites; biochemical evolution; biotechnology; eukaryote; fluorescent dye /probe; functional /structural genomics; fusion gene; gene expression; genetic enhancer element; genetic manipulation; genetic regulation; genetic regulatory element; regulatory gene; systematic biology; transcription factor; transposon /insertion element

DESCRIPTION (provided by applicant): Deciphering the organization of noncoding sequences involved in the regulation of eukaryotic gene expression, both structurally and functionally, is a major, post-genome sequence challenge. We believe that developing an understanding of evolutionary processes acting on these sequences, and establishing evolutionary rules governing the relationship between structure/function and evolutionary constraint, will be critical to meeting this challenge. Our proposal is to experimentally dissect evolved changes in a model cis-regulatory element, the Drosophila even-skipped stripe 2 element, one of the best functionally characterized of all eukaryotic enhancer sequences. Our experiments will allow us to determine the functional importance of evolved changes in the sequences of regulatory protein binding sites within the element, the functional importance of changes in spacing between binding sites, and the possible co-evolutionary interaction of the two. In addition, we describe the technical capability to conduct these evolutionary genetic analyses of interspecific differences in the genetic background of each species under investigation, providing the first opportunity to critically examine the importance of trans-acting factor coevolution in the evolution of gene regulation. These experiments will benefit the analysis of eukaryotic genome structure/function and will aid work to decipher the controls of human gene expression.

描述（由申请人提供）：解密非编码的组织 与真核基因表达调节有关的序列，两者都 在结构和功能上，是主要的，后的后序列序列挑战。我们 相信对行动的进化过程的理解 这些序列，并建立有关关系的进化规则 在结构/功能和进化约束之间，对 应对这个挑战。我们的建议是实验剖析 果蝇均匀的条纹2中的模型顺序调节元件的变化2 元素，所有真核增强剂的功能最佳特征之一 序列。我们的实验将使我们能够确定功能重要性 调节蛋白结合位点序列的进化变化 元素是绑定之间间距变化的功能重要性 位点，以及两者的可能共同相互作用。另外，我们 描述进行这些进化遗传的技术能力 分析每个物种的遗传背景中种间差异 正在调查中，提供了第一个批判性检查的机会 跨作用因子协同进化在基因进化中的重要性 规定。这些实验将有益于真核基因组的分析 结构/功能，将有助于破译人类基因的控制 表达。