Mechanisms of Dynamic Chromatin Looping During Differentiation - Common Fund Data Supplement

分化过程中动态染色质循环的机制 - 共同基金数据补充

• 批准号: 9983342
• 负责人: Douglas H. Phanstiel
• 金额: $ 14.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-19 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983342
• 关键词: 3-Dimensional; Address; Affect; Area; Base Pairing; Biological; Biological Process; Chromatin; Chromatin Loop; Chromatin Structure; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Computer Simulation; Computing Methodologies; Data; Data Set; Disease; Enhancers; Event; Funding; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genome; Genomics; Head; Hour; Human Genome; Innate Immune Response; Macrophage Activation; Maps; Methods; Modeling; Multiomic Data; Nature; Pattern; Play; Process; Regulatory Element; Resources; Role; Techniques; Technology; Time; Transcriptional Regulation; United States National Institutes of Health; Untranslated RNA; Work; base; cardiogenesis; cell type; computerized tools; design; experimental study; genetic variant; genome editing; genomic data; human disease; improved; macrophage; multiple omics; novel; response; temporal measurement; tool

Project Abstract This application is being submitted in response to NOT-RM-19-009. Enhancers are context-specific regulatory elements that play a critical role in transcriptional control of biological processes such as differentiation and activation; however, the dynamic nature of enhancers and their ability to affect genes over great distances have made identifying the targets of enhancers an enormous challenge. The 4D Nucleome project has made great strides towards understanding enhancers and their role in gene regulation and has generated a variety of data sets characterizing enhancers, 3D chromatin structure, and gene transcription across biological time courses. This has created a dire need for computational methods designed specifically for, and taking full advantage of, the temporal aspects of existing and forthcoming time-course data sets generated by the 4D nucleome project and others. Here we propose a computational approach to predict enhancer-gene pairs by leveraging the temporal patterns of enhancer strength, chromatin contacts, and gene expression. We will apply this method to multi-omic time courses of cellular activation and differentiation to identify putative enhancers and their target genes. We will then validate select enhancer-gene pairs using genome editing and qPCR. This work will identify novel context-specific enhancer-gene pairs and produce a new computational tool to extract these pairings from forthcoming multi-omic time-course data sets from the 4D Nucleome project.

项目摘要