MECHANISMS OF DYNAMIC CHROMATIN LOOPING DURING DIFFERENTIATION

分化过程中动态染色质环的机制

• 批准号: 10415986
• 负责人: Douglas H. Phanstiel
• 金额: $ 38.32万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415986
• 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.

摘要 染色质环跨越数十至数百个酶连接启动子远端调控元件，如 它们的靶基因的启动子的增强子。这些环中的许多是细胞类型特异性的， 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 我们探测这些环的能力的进步大大提高了我们对分子生物学的认识。 DNA环的组成部分;然而，细胞周期中DNA环变化的机制和功能， 差异性仍然知之甚少。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环， 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）绘制环路， 事件，以及在细胞分化过程中具有时间分辨率的基因转录，（2）发育和 应用新的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 在分化过程中形成的环的机制研究。这项研究的结果将决定 在分化过程中DNA环形成的范围和一般原则，为研究 基因调控共同体，并阐明非编码人类基因组的功能。