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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要该申请是针对NOT-RM-19-009提交的。增强剂是特定于上下文的在生物学过程中的转录控制中起关键作用的监管元素，例如分化和激活；但是，增强剂的动态性质及其影响基因的能力在很大的距离上，确定增强剂的目标成为巨大的挑战。这 4D核心项目已取得了长足的进步，以了解增强子及其在基因中的作用调节，并生成了表征增强剂的各种数据集，3D染色质结构，和跨生物时间课程的基因转录。这产生了对计算的迫切需求专门设计并充分利用现有和的时间方面的方法 4D核心项目和其他人生成的即将到来的时间课程数据集。我们在这里提出一种计算方法来通过利用时间模式来预测增强子基因对增强剂强度，染色质接触和基因表达。我们将把这种方法应用于多摩变细胞激活和分化的时间课程，以识别推定的增强剂及其目标基因。然后，我们将使用基因组编辑和QPCR验证选择的增强子基因对。这项工作将识别新颖的上下文特定增强子基因对，并生成一种新的计算工具来提取这些来自4D Nucleome项目的多词时时间课程集的配对。