MECHANISMS OF DYNAMIC CHROMATIN LOOPING DURING DIFFERENTIATION

分化过程中动态染色质环的机制

• 批准号: 10198946
• 负责人: Douglas H. Phanstiel
• 金额: $ 38.33万
• 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/10198946
• 关键词: 3-Dimensional; Architecture; Bioinformatics; Cells; Chromatin; Chromatin Loop; Communities; Computer software; Development; Distal; Enhancers; Event; Gene Expression Regulation; Genes; Genetic Transcription; Genomics; Goals; Human Development; Human Genome; Investigation; Knowledge; Link; Mission; Molecular; Output; Play; Regulatory Element; Research; Role; Structure; Technology; Transcriptional Regulation; Untranslated RNA; base; cell type; genome editing; promoter; temporal measurement; tool

ABSTRACT Chromatin loops spanning tens to hundreds of kilobases link promoter-distal regulatory elements such as enhancers to the promoters of their target genes. Many of these loops are cell-type specific and are thought to play a critical role in transcriptional control during cellular differentiation and human development. Recent progress in our ability to detect these loops has significantly advanced our knowledge regarding the molecular components of DNA loops; however, the mechanisms and functions of changes in DNA looping during cellular differentiation remain poorly understood. The goals of our research are to identify the mechanisms through which cells establish new loops during cellular differentiation and to determine how the resulting structures contribute to altered transcriptional output. We will accomplish these goals by: (1) mapping loops, regulatory events, and gene transcription with temporal resolution during cellular differentiation, (2) developing and applying new software to identify and visualize dynamic looping events, and (3) performing targeted mechanistic investigations of loops formed during differentiation. The results of this research will determine both the scope and general principles of DNA loop formation during differentiation, provide new tools for the gene regulation community, and illuminate the functions of the non-coding human genome.

抽象的 跨越数十至数百千碱基的染色质环连接启动子-远端调控元件，例如 增强子及其靶基因的启动子。许多这些循环是细胞类型特异性的，并且被认为 在细胞分化和人类发育过程中的转录控制中发挥关键作用。最近的 我们检测这些环的能力的进步极大地提高了我们关于分子的知识 DNA环的组成部分；然而，细胞过程中 DNA 循环变化的机制和功能 差异化仍然知之甚少。我们研究的目标是通过以下方式确定机制： 哪些细胞在细胞分化过程中建立新的循环并确定所得结构如何 有助于改变转录输出。我们将通过以下方式实现这些目标：(1) 映射循环、监管 细胞分化过程中事件和具有时间分辨率的基因转录，(2) 发育和 应用新软件来识别和可视化动态循环事件，以及（3）执行有针对性的 对分化过程中形成的环的机制研究。这项研究的结果将决定 分化过程中 DNA 环形成的范围和一般原理，为 基因调控群落，并阐明非编码人类基因组的功能。