PRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOME

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， 对大多数人类基因组功能的了解是有限的。监管信息映射 尤其重要，因为大多数（>85%）与人类疾病相关的常见变异都位于 编码区。ENCODE的前几个阶段对绘制 基因组中的调控元件，但还有更多的工作要做，包括映射 调节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。在我们斯坦福大学 ENCODE生产中心的监管区域地图，我们计划使用的技术，我们 已经开发出使用以下方法在五种主要细胞系中绘制大多数转录因子（TF）的结合位点： 标记的TF的染色质免疫沉淀。进一步扩大监管要素目录 通过分析这些细胞系中的开放染色质区域以及来自这些细胞系的各种组织和细胞类型， 正常和患病的人类受试者都同意开放获取。最后，我们将地图打开 来自这些类型的生物样品的单细胞中的染色质区域。这些研究将大大扩展 人类基因组调控区目录。将数据快速存入ENCODE数据 协调中心（DCC）将确保快速公开发布。我们希望这些数据和细胞系 该中心产生的信息将成为广大科学界的宝贵资源。

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 acheived, 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 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.