Expanding the catalog of chromatin regulatory elements in the human genome

人类基因组由数十万个功能性DNA元件调节，这些元件在发育和疾病中发挥关键作用，但仍然知之甚少。因此，功能性DNA元件的全面鉴定和表征是对人类健康具有重大影响的基本目标。基因组DNA被组织成染色质，一种由DNA、RNA和蛋白质组成的高级结构。染色质作图技术已经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。绘图使得能够系统地注释不同类型的功能元件，包括启动子、增强子和沉默子，以及与健康和疾病中的染色质组织和基因组调控相关的新发现。 拟建的ENCODE数据生产中心旨在通过染色质的蛋白质、DNA和RNA成分的生产图谱来大大扩展人类基因组中功能元件的目录。高通量管道将用于绘制组蛋白修饰，染色质调节蛋白和非编码RNA结合相互作用。这些管道将应用于指定的ENCODE细胞系，胚胎干（ES）细胞和衍生物，诱导多能干（iPS）细胞和表型多样的人类组织。关键的组蛋白修饰也将在来自多个个体的代表性细胞和组织类型中进行映射，以解决染色质景观中个体间变异的程度和意义及其与遗传背景的关系。 这些多维数据集将通过创新的计算算法进行整合，以识别决定染色质状态和功能元件活性的序列，基序，变体和调控相互作用。因此，拟议的项目将大大增加ENCODE目录中功能性DNA元件的数量、分辨率和精度，并明确定义介导人类基因组中染色质状态和调控的因果序列和物理相互作用。 所有数据将迅速公布，并免费提供给科学界。

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.