Arabidopsis 2010: High-resolution Mapping of Regulatory DNA

拟南芥 2010：调控 DNA 的高分辨率图谱

• 批准号: 0929046
• 负责人: John Stamatoyannopoulos
• 金额: $ 201.15万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0929046&HistoricalAwards=false
• 关键词: Arabidopsis; 2010; resolution; Mapping; Regulatory

The genome of an organism encodes not only genes and their RNA and protein products, but also the integrated programs that define when, where, and to what extent different genes are activated or silenced. At the DNA level, gene regulatory signals are encoded by regulatory elements that comprise clustered recognition sites for DNA binding proteins. However, the location and function of the vast majority of Arabidopsis regulatory sequences is currently obscure. In this project, novel high-throughput epigenomic technologies--Digital DNaseI Mapping and Digital Genomic Footprinting--will be applied to map and characterize regulatory DNA across the A. thaliana genome at nucleotide resolution. These technologies are capable of mapping the locations of regulatory DNA sequences, and delineating the specific sites of regulatory factor binding within such regions. Because gene regulatory programs vary widely both between different cell types and within a cell type during differentiation, the project will encompass multiple developmental stages and tissues of a reference strain. As sessile organisms, plants integrate many cues into appropriate developmental and stress responses, most of which rely on major re-programming gene regulatory responses. Regulatory DNA involved in such responses will therefore be mapped through study of standard stress conditions. At the population level, most phenotypic variation is likely to derive from non-coding genetic variation. By systematically extending maps of regulatory DNA across both diverse A. thaliana accessions and related species, the project will expose relationships between genotypic variation and gene regulatory programs on a genome-wide scale. The resulting data will provide unprecedented insight into endogenous and environmentally-responsive plant regulatory programs, and will significantly accelerate the identification of functional non-coding variation underlying relevant phenotypic variation. Broader impacts. This project has the potential to change fundamentally the landscape of gene regulation research in A. thaliana and in plants generally, both as it applies to basic mechanisms and in its application to solve diverse quantitatively varying phenotypes. The availability of comprehensive, high-resolution regulatory DNA maps for A. thaliana stages, tissues, treatments, accessions, and evolutionarily related species will immediately bring A. thaliana to the forefront of regulatory genomics, and will provide a powerful attraction for bringing dynamic new investigators to the field. The comprehensive annotation of A. thaliana regulatory regions and transcription factor binding sites targeted under this project will be of use to the entire plant biology community, and will develop significant data resources that will potentiate experimental approaches to determining gene function. The project will foster the advancement of plant regulatory genomics through rapid dissemination of data to the public domain via genomic databases as well as relevant analytical tools to assist in its utilization by diverse investigators. The project will also encompass a significant educational component aimed at training next-generation leaders in plant regulatory genomics, and recruitment and training of talented undergraduate and graduate scientists from diverse backgrounds.

生物体的基因组不仅编码基因及其RNA和蛋白质产物，还编码定义何时、何地以及在何种程度上激活或沉默不同基因的整合程序。在DNA水平，基因调控信号由调控元件编码，所述调控元件包含DNA结合蛋白的成簇识别位点。然而，绝大多数拟南芥调控序列的位置和功能目前还不清楚。在这个项目中，新的高通量表观基因组技术-数字DNaseI映射和数字基因组足迹-将被应用于映射和表征跨A.拟南芥基因组的核苷酸分辨率。这些技术能够绘制调控DNA序列的位置，并描绘这些区域内调控因子结合的特定位点。由于基因调控程序在不同细胞类型之间和分化过程中的细胞类型内差异很大，因此该项目将涵盖参考菌株的多个发育阶段和组织。作为固着生物，植物将许多线索整合到适当的发育和胁迫反应中，其中大多数依赖于主要的重编程基因调控反应。因此，通过对标准应激条件的研究，将绘制参与这种反应的调节DNA。在群体水平上，大多数表型变异可能来自非编码遗传变异。通过系统地延伸调控DNA在两种不同的A。该项目将在全基因组范围内揭示基因型变异与基因调控程序之间的关系。由此产生的数据将提供前所未有的洞察内源性和环境响应植物调控程序，并将显着加快相关表型变异的功能性非编码变异的识别。更广泛的影响。该项目有可能从根本上改变A. thaliana和一般植物中，既适用于基本机制，又适用于解决各种数量变化的表型。全面的，高分辨率的调控DNA图谱的可用性A。thaliana阶段，组织，处理，加入，和进化相关的物种将立即带来A。thaliana的基因组学的前沿，并将提供一个强大的吸引力，使充满活力的新的研究人员到外地。对A.本项目针对的拟南芥调控区和转录因子结合位点将对整个植物生物学界有用，并将开发重要的数据资源，加强确定基因功能的实验方法。 该项目将通过基因组数据库和相关分析工具向公共领域快速传播数据，以协助不同研究人员利用数据，从而促进植物调控基因组学的发展。该项目还将包括一个重要的教育组成部分，旨在培训植物调控基因组学的下一代领导人，以及招聘和培训来自不同背景的有才华的本科生和研究生科学家。