PRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOME

人类基因组监管区域图谱制作中心

• 批准号: 10241080
• 负责人: MICHAEL P. SNYDER
• 金额: $ 316.81万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241080
• 关键词: Binding; Binding Sites; Catalogs; Cell Line; Cells; Chromatin; Code; Communities; Consent; Data; Data Coordinating Center; Ensure; Gene Expression; Genome; Human Genome; Individual; Maps; Nucleic Acid Regulatory Sequences; Phase; Production; Regulator Genes; Regulatory Element; Resolution; Resources; Sea; Technology; Tissues; Variant; cell type; chromatin immunoprecipitation; data submission; human DNA; human disease; human subject; transcription factor

ABSTRACT Although our ability to determine the genome sequence of individuals is becoming facile, our understanding of the function of most of the human genome is limited. Mapping of regulatory information is particularly crucial since most (>85%) common variants associated with human disease lie outside of coding regions. Previous phases of ENCODE have made important contributions to the mapping of regulatory elements across the genome, but there is much more to be achieved, including the mapping of regulatory regions across many more tissues and at the resolution of individual cells as well as determining the exact regulators i.e. transcription factors that bind each region. In our Stanford ENCODE Production Center for Mapping of Regulatory Regions, we plan to use technologies that we have developed to map the binding sites for most transcription factors (TFs) in five major cell lines using chromatin immunoprecipitation of tagged TFs. We will further expand the catalog of regulatory elements by analyzing open chromatin regions in these cell lines and a wide variety of tissues and cell types from both normal and diseased human subjects consented for open access. Finally, we will map open chromatin regions and expression in single cells from these types of biosamples. These studies will greatly expand the catalog of regulatory regions in the human genome. The rapid deposition of data into the ENCODE Data Coordinating Center (DCC) will ensure quick public release. We expect the data and cell lines that are generated by this Center will be a valuable resource for the broad scientific community.

抽象的 尽管我们确定个体基因组序列的能力正在变得容易，但我们的理解 大多数人基因组的功能受到限制。尤其是监管信息的映射 至关重要的是，与人类疾病相关的大多数（> 85％）的常见变体都在编码区域之外。 以前的编码阶段为监管元素的映射做出了重要贡献 在整个基因组中 在更多的组织中，在单个细胞的分辨率上以及确切的 调节剂，即结合每个区域的转录因子。在我们的斯坦福大学编码生产中心 监管区域的映射，我们计划使用我们开发的技术来映射绑定 使用染色质免疫沉淀在五个主要细胞系中的大多数转录因子（TF）的位点 标记的TF。我们将通过分析开放染色质区域进一步扩大调节元素的目录 在这些细胞系以及正常和患病的各种组织和细胞类型中 受试者同意开放访问。最后，我们将在单个中绘制开放的染色质区域和表达 这些类型的生物样本中的细胞。这些研究将大大扩展监管区域的目录 人类基因组。数据将数据快速沉积到编码数据协调中心（DCC）将 确保公开发布。我们希望该中心生成的数据和单元线将是 广泛科学界的宝贵资源。