Computing Regulatory DNA by Comparing Genomes

通过比较基因组计算监管 DNA

• 批准号: 1248106
• 负责人: Michael Freeling
• 金额: $ 88.2万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-11-01 至 2015-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1248106&HistoricalAwards=false
• 关键词: Computing; Regulatory; DNA; Comparing; Genomes

PI: Michael Freeling (University of California - Berkeley)This two year project leverages previous work and uses computational tools, along with published sequence and data on levels of mRNA, to hypothesize specific function for noncoding sequences in higher plants. The project takes advantage of the recent release of two important paleopolyploid genomes, maize and Brassica rapa (Chinese cabbage). Having diverged approximately 12 million years ago, each of these ancient polyploids has close relative genomes that can serve as outgroups - sorghum and the other grasses for maize and Arabidopsis, and several recently sequenced crucifers for the cabbages. There are four objectives with the goal of developing a better understanding of the function of enhancers and cis-acting modules, those sequences that regulate gene expression in plants: 1) to develop a new application for CoGe that brings motifs and transcription factor binding sites into view when comparing the sequences of chromosomal segments. CoGe is a popular, public toolbox for visualizing and comparing sequences; 2) to discover genes with new regulatory capabilities by finding rare cases of new sequence corresponding to new patterns of expression. Finding genes that switch their patterns of genome dominance should relate to this aim; 3) to find the means by which plant regulatory DNA evolves into non-detectability without losing its function, a process known as "binding site turnover" in mammals; and, 4) to elucidate enhancer evaluation in plants by using the natural process of fractionation mutagenesis to generate specific sequences with specific functions using computational data only. Hypotheses based on the predicted enhancers will be tested using transient and stable expression of engineered reporter genes.Broader aims of the project include a summer internship program for underserved, local high school students, and continued development of the popular CoGe website (http://genomevolution.org/CoGe/) containing applications that help find meaning when genes and genomes are compared. This project will host one or two students each summer. Additionally, this project involves improvements to the CoGe suite of free, on-the fly applications now powered by iPlant (http://www.iplantcollaborative.org/) that will provide broad access to the broader scientific community.

主要研究者：Michael Freeling（加州-伯克利大学）这个为期两年的项目利用以前的工作，并使用计算工具，沿着公布的序列和mRNA水平的数据，假设高等植物中非编码序列的特定功能。 该项目利用了最近公布的两个重要的古多倍体基因组，玉米和芜菁（大白菜）。 这些古老的多倍体在大约1200万年前分化，每一个都有近缘的基因组，可以作为外类群-高粱和其他禾本科植物的玉米和拟南芥，以及几个最近测序的十字花科植物的卷心菜。为了更好地理解增强子和顺式作用模块的功能，有四个目标，这些序列调节植物中的基因表达：1）开发CoGe的新应用，当比较染色体片段的序列时，将基序和转录因子结合位点纳入视野。 CoGe是一个流行的公共工具箱，用于可视化和比较序列; 2）通过发现与新表达模式对应的新序列的罕见情况来发现具有新调控能力的基因。 3）找到植物调节DNA进化到不可检测状态而不丧失其功能的途径，这一过程在哺乳动物中被称为“结合位点转换”;并且，在本发明中，四、通过使用分级诱变的天然过程，使用计算数据产生具有特定功能的特定序列，只. 基于预测的增强子的假设将使用工程报告基因的瞬时和稳定表达进行测试。该项目更广泛的目标包括为服务不足的当地高中生提供暑期实习计划，以及继续开发流行的CoGe网站（http：//genomevolution.org/CoGe/），该网站包含有助于在比较基因和基因组时找到意义的应用程序。 这个项目每年夏天都会接待一到两名学生。 此外，该项目还涉及改进CoGe套件的免费、即时应用程序，这些应用程序现在由iPlant（http：//www.iplantcollaborative.org/）提供支持，将为更广泛的科学界提供广泛的访问。