CAREER: Mechanisms of cis-/trans-promoter competition in Drosophila

职业：果蝇顺式/反式启动子竞争机制

• 批准号: 1349779
• 负责人: Jack Bateman
• 金额: $ 79.74万
• 依托单位: Bowdoin College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-15 至 2019-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1349779&HistoricalAwards=false
• 关键词: CAREER; Mechanisms; cis; trans; promoter

Intellectual Merit:Physical contacts between chromosomes, known as interchromosomal interactions, are observed in interphase nuclei of diverse species. In some cases, these interactions allow regulatory elements to act in trans, modulating the expression of genes encoded on a separate chromosome held in close proximity. The advent of high-throughput genome-wide analyses of chromosomal conformations has vastly accelerated the rate at which interchromosomal interactions can be cataloged; however, the functional characterization of their genetic consequences has lagged behind. This CAREER project helps to fill the "function gap" by developing a comprehensive understanding of how a gene expression enhancer will behave when it encounters potential gene regulatory promoters on separate but nearby chromosomes. The experiments center on the creation of transgenic Drosophila carrying various fluorescent reporters that act as readouts for the impacts of interchromosomal interactions on gene expression. These experiments will provide a better understanding of the parameters governing enhancer action in trans, providing information on how the spatial organization of the nucleus impacts enhancer-promoter specificity. Broader Impacts:The education plan of this project is focused on expanding research opportunities and hands-on experience in genetics and molecular biology for undergraduate students. Specifically, the project will 1) develop a research-based lab module for an undergraduate genetics course, 2) offer an annual workshop for undergraduate students from a local community college, 3) partner with an existing program that introduces research opportunities to students from underrepresented groups, and 4) provide opportunities for independent research for undergraduates from diverse backgrounds.

智力优点：在多种物种的相间核中观察到染色体之间的物理接触，称为染色体相互作用。在某些情况下，这些相互作用允许调节元素在反式中起作用，调节在靠近近端的单独染色体上编码的基因的表达。染色体构象全基因组的高通量基因组分析的出现极大地加速了染色体相互作用的速度。然而，其遗传后果的功能表征落后了。通过对基因表达增强子在遇到潜在的基因调节启动子上的潜在基因调节启动子在单独但附近的染色体上遇到潜在的基因调节启动子时，该职业项目有助于填补“功能差距”。实验集中在创建携带各种荧光记者的转基因果蝇的创造，这些荧光记者充当了染色体相互作用对基因表达的影响的读数。这些实验将更好地理解有关跨性别者中管理增强剂作用的参数，从而提供有关核的空间组织如何影响增强子启动器特异性的信息。更广泛的影响：该项目的教育计划着重于扩大本科生遗传学和分子生物学方面的研究机会和实践经验。具体而言，该项目将为本科遗传学课程开发一个基于研究的实验室模块，2）为来自当地社区学院的本科生提供年度研讨会，3）与现有计划合作，该计划为来自代表性不足的小组的学生介绍研究机会，4）为来自不同背景的独立研究提供了机会。