High-throughput sequencing of chromatin regulatory elements

这个ENCODE联盟项目旨在以系统的方式识别和分类人类基因组中的染色质调节元件。这一目标正在通过应用染色质方法和超高通量测序来实现，以获得反映组蛋白修饰和染色质蛋白在给定细胞类型中的分布的全基因组图谱。通过分析多种细胞类型，该项目将建立一个日益全面的染色质调控元件目录，并深入了解它们的细胞类型特性。尽管染色质有几十种不同的修饰和许多其他结构成分，但用现有的抗体和试剂只能测量到一小部分。这项补充请求的基本原理是，能够在整个基因组中描述这些额外的修饰和蛋白质，将增强我们对ENCODE阐明的功能元件的结构和调节的理解，并揭示尚不清楚的其他元件。申请的资金将用于筛选数十个额外的染色质表位，目的是为全基因组图谱确定合适的试剂和方法。将通过传统方法和高通量技术相结合的方式进行筛选。通过这一过程确定的试剂然后将在现有的ENCODE管道中应用，以表征新表位的全基因组分布及其与已知或新的调节元件的关系。 染色质调节在人类发育和疾病中具有广泛的重要性。对人类基因组中染色质调控元件的系统鉴定和鉴定将为深入了解染色质的结构和功能提供有价值的见解，并为染色质、基因组学、癌症等许多领域的研究人员提供资源。一旦可靠性得到确认，在拟议项目范围内收集的所有数据将在出版前提供给更大的科学界。 2.

This ENCODE consortium project aims to identify and classify chromatin regulatory elements in the human genome in systematic fashion. This goal is being pursued through the application of chromatin methods and ultra high-throughput sequencing to acquire genomewide maps that reflect the distributions of histone modifications and chromatin proteins in a given cell type. By assaying multiple cell types, the project will build an increasingly comprehensive catalog of chromatin regulatory elements and gain insight into their cell typespecificities. Although there are dozens of different modifications and many other structural components in chromatin, only a fraction can be measured with existing antibodies and reagents. The rationale of this supplement request is that an ability to characterize these additional modifications and proteins as they occur across the genome would augment our understanding of the structure and regulation of functional elements elucidated by ENCODE, and reveal additional elements of yet unknown significance. Requested funds would be use to screen dozens of additional chromatin epitopes with the goal of identifying suitable reagents and methods for genomewide mapping. The screens will be pursued through a combination of conventional methods and high-throughput techniques. Reagents identified through this process will then be applied within the existing ENCODE pipeline to characterize genomewide distributions of the novel epitopes and their relationships to known or novel regulatory elements. Chromatin regulation is of wide-ranging importance in human development and disease. The proposed systematic identification and characterization of chromatin regulatory elements in the human genome will offer valuable insight into the structure and function of chromatin, and provide a resource for investigators in chromatin, genomics, cancer and many other fields of research. All data collected in the context of the proposed project will be made available pre-publication to the greater scientific community as soon as reliability has been confirmed. 2.