Digital DNaseI mapping and footprinting of the mouse genome

小鼠基因组的数字 DNaseI 绘图和足迹

• 批准号: 7854853
• 负责人: MARK T GROUDINE
• 金额: $ 67.5万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854853
• 关键词: Adult; Algorithms; Animal Model; Binding Sites; Cataloging; Catalogs; Cell Line; Cells; Chromatin; Computer Analysis; Coupled; DNA; DNA-Binding Proteins; Data; Data Quality; Development; Elements; Embryo; Exhibits; Fetal Tissues; Generations; Genetic; Genetic Polymorphism; Genome; Genomics; Goals; Harvest; Hematopoietic; Histocompatibility Testing; Human; Human Genome; Indium; Knowledge; Maps; Modeling; Mouse Strains; Mus; Nucleic Acid Regulatory Sequences; Nucleotides; Organ; Pattern; Production; Public Domains; Public Health; RNA; Reading; Research Infrastructure; Resolution; Resources; Sentinel; Site; Solid; Sorting - Cell Movement; Staging; Surveys; Technology; Tissue Sample; Tissues; analog; base; cell type; cost; digital; embryonic stem cell; genome-wide; high standard; human disease; insight; mouse genome; novel; public health relevance

DESCRIPTION (provided by applicant): The goal of this project is to produce comprehensive, high-definition maps of mouse regulatory DNA marked by DNaseI hypersensitive sites to parallel the human catalogue currently under production by the ENCODE Project. Digital DNaseI technology enables efficient genome-wide mapping of accessible chromatin and DNaseI hypersensitive sites. The core regions of DNaseI hypersensitive sites are constitutively populated by regulatory factor binding sites, the nucleotide-resolution footprints of which may be systematically exposed on a genome-wide scale by ultra-deep sequencing. DNaseI hypersensitive sites exhibit marked cell-type variability; accordingly, production of a comprehensive catalog will require surveying a wide range of cell types. Cell types targeted under this proposal include murine analogues of the ENCODE Tier 1 and Tier 2 common reference cell lines; a broad spectrum of primary adult tissues; embryonic stem cells; and sentinel tissues amenable to sequential temporal profiling during development. The production of a parallel, high-quality, high-resolution compendium of mouse regulatory DNA will greatly enhance the value of the human ENCODE project and will provide a rich independent and unique resource for evolutionary, functional, and model organism genomics. PUBLIC HEALTH RELEVANCE: Relevance to Public Health Understanding the genetic basis of human disease requires detailed knowledge of the functional elements of the human genome which may be subject to polymorphism. The ENCODE Project seeks to identify all of the functional elements in the human genome, and present project seeks to greatly increase the value of the ENCODE data by providing a parallel catalogue of regulatory DNA in the mouse genome. This project is therefore expected to provide key insights into the importance of elements in the human genome, and to provide an unprecedented resource for rational functional modeling of human disease in the mouse.

描述（由申请人提供）：该项目的目标是产生由DNaseI超敏位点标记的小鼠调节DNA的全面的、高清晰度的图谱，以与ENCODE项目目前正在生产的人类目录平行。数字化DNaseI技术可实现染色质和DNaseI超敏感位点的全基因组高效定位。DNaseI超敏感位点的核心区域由调节因子结合位点组成，其核苷酸分辨率足迹可以通过超深度测序在全基因组范围内系统地暴露。DNaseI超敏位点表现出明显的细胞类型变异性;因此，产生一个全面的目录将需要调查广泛的细胞类型。该提案所针对的细胞类型包括ENCODE Tier 1和Tier 2常见参考细胞系的鼠类似物;广泛的原代成体组织;胚胎干细胞;以及在发育期间适合于顺序时间分析的哨兵组织。一个平行的，高质量的，高分辨率的小鼠调控DNA纲要的生产将大大提高人类ENCODE项目的价值，并将提供丰富的独立和独特的资源，进化，功能和模式生物基因组学。 公共卫生相关性：要了解人类疾病的遗传基础，就需要详细了解人类基因组中可能存在多态性的功能元件。ENCODE项目旨在识别人类基因组中的所有功能元件，本项目旨在通过提供小鼠基因组中调控DNA的平行目录来大大增加ENCODE数据的价值。因此，该项目有望为人类基因组中元素的重要性提供关键见解，并为小鼠中人类疾病的合理功能建模提供前所未有的资源。