Digital DNaseI mapping and footprinting of the mouse genome

描述(由申请人提供)：该项目的目标是制作由DNaseI超敏感部位标记的全面、高清晰度的小鼠调节DNA图谱，以与ENCODE项目目前正在制作的人类目录相平行。数字DNaseI技术能够有效地绘制可访问的染色质和DNaseI超敏部位的全基因组图谱。DNaseI超敏位点的核心区由调控因子结合位点组成，其核苷酸分辨足迹可能通过超深度测序在全基因组范围内系统地暴露出来。DNaseI超敏感部位表现出明显的细胞类型变异性；因此，制作一份全面的目录将需要对广泛的细胞类型进行调查。这项建议针对的细胞类型包括ENCODE Tier 1和Tier 2常见参考细胞系的小鼠类似物；广泛的初级成人组织；胚胎干细胞；以及在发育过程中可按顺序进行时间特征分析的前哨组织。一个平行的、高质量、高分辨率的小鼠调控DNA纲要的产生将极大地提高人类ENCODE计划的价值，并将为进化、功能和模式生物基因组学提供丰富的独立和独特的资源。 公共卫生相关性：与公共卫生的相关性了解人类疾病的遗传基础需要详细了解人类基因组的功能元件，这些元件可能受到多态的影响。ENCODE项目寻求识别人类基因组中的所有功能元件，而Present项目寻求通过提供小鼠基因组中调控DNA的平行目录来极大地增加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的见解，并为在小鼠中对人类疾病进行合理的功能建模提供前所未有的资源。

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.