Expanding the catalog of chromatin regulatory elements in the human genome

扩大人类基因组中染色质调控元件的目录

基本信息

批准号：
8902243
负责人：
BRADLEY Evan BERNSTEIN
金额：
$ 157.65万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-21 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8902243
关键词：
Address Antibodies Base Sequence Beryllium Binding Biological Assay Biology Cataloging Catalogs Cell Line Cells ChIP-seq Characteristics Chromatin Chromatin Structure Communities Complex Computational algorithm Coupled DNA Data Data Set Development Disease ES Cell Line Elements Enhancers Genes Genetic Genome Genomic DNA Genomics Germ Layers Goals Haplotypes Health Higher Order Chromatin Structure Histocompatibility Testing Histones Human Human Genome Indium Individual Location Malignant Neoplasms Mammalian Cell Maps Mediating Methods Modeling Modification Oligonucleotides Output Play Production Proteins RNA RNA Binding RNA immunoprecipitation sequencing Reagent Regulation Regulatory Element Research Resolution Resources Role Sampling Specificity Stem cells Surveys Technology Testing Tissues Untranslated RNA Variant Vision base cell type developmental disease epigenetic regulation genetic regulatory protein genome-wide histone modification human disease human tissue improved induced pluripotent stem cell innovation insight pluripotency promoter protein complex transcription factor

项目摘要

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.

人类基因组受到数十万个功能性DNA元素在发育和疾病中起关键作用的功能性DNA元素的调节，但仍知之甚少。因此，功能性DNA元件的全面识别和表征是对人类健康的主要影响的基本目标。基因组DNA被组织成染色质，这是由DNA，RNA和蛋白质组成的高阶结构。染色质映射技术已成为识别功能性DNA元素的强大手段，该功能与特征染色质结构相关。映射使各种功能元素的系统注释（包括启动子，增强剂和消音器）以及与染色质组织和健康和疾病中的基因组调节有关的新发现。所提出的编码数据生产中心旨在通过蛋白质，DNA和RNA成分的生产映射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编码细胞系，胚胎干细胞和衍生物，诱导多能茎（IPS）细胞以及表型多样的人体组织。关键组蛋白的修饰还将在来自多个个体的代表性细胞和组织类型中映射，以解决染色质景观中个体间变异的程度和重要性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集成，以识别决定染色质状态和功能元素活动的序列，基序，变体和调节相互作用。因此，所提出的项目将大大增加编码目录中功能DNA元素的数量，分辨率和精度，并明确定义了介导人类基因组中染色质状态和调节的因果序列和物理相互作用。所有数据将迅速发布并免费提供给科学界。