Expanding the catalog of chromatin regulatory elements in the human genome

人类基因组由成千上万的功能性DNA元件调控，这些元件在发育和疾病中起着关键作用，但人们对它们的了解仍然很少。因此，对功能性DNA元素的全面鉴定和表征是一个对人类健康具有重大影响的基本目标。基因组DNA由染色质组成，染色质是由DNA、RNA和蛋白质组成的高阶结构。染色质定位技术已成为鉴定与特征染色质结构相关的功能DNA元件的有力手段。绘制基因组图谱使得系统地标注不同类型的功能元件，包括启动子、增强子和沉默子，以及在健康和疾病中与染色质组织和基因组调控相关的新发现成为可能。

The human genome is regulated by hundreds of thousands of functional DNA elements that play pivotal roles in development and disease, yet remain poorly understood. Comprehensive identification and characterization of functional DNA elements is thus an essential goal with major implications for human health. Genomic DNA is organized into chromatin, a higher-order structure composed of DNA, RNA and proteins. Chromatin mapping technologies have emerged as a powerful means for identifying functional DNA elements, which are associated with characteristic chromatin structures. Mapping has enabled the systematic annotation of diverse types of functional elements, including promoters, enhancers and silencers, and new discoveries related to chromatin organization and genome regulation in health and disease. The proposed ENCODE data production center aims to vastly expand the catalog of functional elements in the human genome through production mapping of Protein, DNA and RNA constituents of chromatin. High-throughput pipelines will be used to map histone modifications, chromatin regulatory proteins and non-coding RNA binding interactions. These pipelines will be applied to designated ENCODE cell lines, embryonic stem (ES) cells and derivatives, induced pluripotent stem (iPS) cells and phenotypically diverse human tissues. Key histone modifications will also be mapped in representative cell and tissue types from multiple individuals, in order to address the extent and significance of inter-individual variation in chromatin landscapes and their relationships to genetic background. These multi-dimensional datasets will be integrated through innovative computational algorithms to identify sequences, motifs, variants and regulatory interactions that dictate chromatin state and functional element activity. Thus, the proposed project will dramatically increase the number, resolution and precision of functional DNA elements in the ENCODE catalog, and explicitly define causal sequences and physical interactions that mediate chromatin states and regulation in the human genome. All data will be rapidly released and made freely available to the scientific community.