The molecular mechanisms and functional significance of gene positioning

项目摘要 了解细胞对环境信号转录反应的分子控制 对了解环境、衰老和生活方式如何影响生理至关重要。我的实验室发现 基因的位置由细胞主动控制，这影响了几个基因的转录 方式。虽然我们在简单的发芽酵母中研究了这种现象，但它在更复杂的酵母中是保守的 动物，包括人类。我们最近发现，大多数转录因子控制着 基因与核孔复合体的相互作用，影响基因的空间排列 以及染色体之间的相互作用。此外，我们已经表明，与全国人大的这种互动可以 要么促进更强的转录，要么改变染色质结构，以平衡基因未来的表达。 因此，转录因子介导的针对NPC的靶向可能在两个空间上都有广泛的影响 基因组和基因表达的组织。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。

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.