The molecular mechanisms and functional significance of gene positioning

基因定位的分子机制及功能意义

• 批准号: 10669133
• 负责人: Jason Hays Brickner
• 金额: $ 55.05万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669133
• 关键词: Aging; Animals; Biological Models; Cell Nucleus; Cells; Chromatin Structure; Chromosomes; Complex; Environment; Future; Gene Expression; Gene Order; Genes; Genetic Transcription; Genome; Goals; Human; Life Style; Mediating; Molecular; Nuclear Pore Complex; Physiology; Saccharomycetales; Signal Transduction; Transcriptional Regulation; Work; gene interaction; response; transcription factor; yeast genome

Project Summary Understanding the molecular control of transcriptional responses of cells to environmental signals is essential to understand how environment, aging and lifestyle impact physiology. My lab has discovered that the position of genes is actively controlled by cells and that this impacts transcription in several ways. Although we study this phenomenon in the simple budding yeast, it is conserved to more complex animals, including humans. We recently showed that a majority of transcription factors control the interaction of genes with the Nuclear Pore Complex (NPC), impacting the spatial arrangement of genes and the interaction of chromosomes. Furthermore, we have shown that this interaction with the NPC can either promote stronger transcription and alter chromatin structure to poise genes for future expression. Thus, transcription factor-mediated targeting to the NPC likely has broad effects on both the spatial organization of the genome and gene expression. The goals of this work are to determine the molecular mechanisms by which transcription factors and NPCs spatially arrange the yeast genome and to understand how these interactions impact gene expression and chromatin structure.

项目摘要 了解细胞对环境信号的转录反应的分子控制， 了解环境、衰老和生活方式如何影响生理学至关重要。我的实验室发现 基因的位置是由细胞主动控制的，这影响了几种细胞的转录， 的方式虽然我们在简单的芽殖酵母中研究这种现象， 动物，包括人类。我们最近发现，大多数转录因子控制着转录因子的表达。 基因与核孔复合体（NPC）的相互作用，影响基因的空间排列 和染色体的相互作用。此外，我们已经表明，这种与NPC的相互作用可以 要么促进更强的转录，要么改变染色质结构，以使基因为未来的表达做好准备。 因此，转录因子介导的靶向NPC可能对空间分布和细胞周期都有广泛的影响。 基因组的组织和基因表达。这项工作的目标是确定分子 转录因子和NPC在空间上排列酵母基因组的机制， 了解这些相互作用如何影响基因表达和染色质结构。