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.

摘要 尽管我们确定个体基因组序列的能力变得越来越容易，但我们的理解 大多数人类基因组的功能是有限的。监管信息的映射特别重要， 这是至关重要的，因为与人类疾病相关的大多数（>85%）常见变异位于编码区之外。 ENCODE的前几个阶段为绘制监管要素做出了重要贡献 但还有更多的工作要做，包括绘制调控区域， 在更多的组织和单个细胞的分辨率，以及确定确切的 调节因子，即结合每个区域的转录因子。在我们的斯坦福大学ENCODE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法， 标记的TF。我们将通过分析开放的染色质区域来进一步扩大调控元件的目录 在这些细胞系以及来自正常人和患病人的多种组织和细胞类型中 受试者同意开放获取。最后，我们将绘制开放的染色质区域，并在单个 从这些类型的生物样本中提取细胞。这些研究将极大地扩展监管区域的目录， 人类基因组将数据快速存入ENCODE数据协调中心（DCC）， 确保迅速公开释放。我们希望这个中心产生的数据和细胞系将是一个 这是广大科学界的宝贵资源。