DNA zip codes and the spatial organization of the yeast genome

DNA 邮政编码和酵母基因组的空间组织

• 批准号: 9551010
• 负责人: Jason Hays Brickner
• 金额: $ 30.89万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9551010
• 关键词: Binding; Binding Sites; Cell Nucleus; Chromatin Structure; Chromosomes; Code; DNA; DNA-Binding Proteins; Elements; Enzymes; Gene Cluster; Gene Expression; Gene Order; Gene Targeting; Genes; Genetic; Genetic Transcription; Genome; Histones; Individual; Interphase Cell; Lead; Mammals; Mediating; Mediator of activation protein; Methodology; Microfluidics; Modeling; Molecular; Monitor; Movement; Nuclear; Nuclear Pore; Nuclear Pore Complex; Nucleoplasm; Play; Pore Proteins; Positioning Attribute; Proteins; Role; Saccharomyces cerevisiae; Testing; Yeasts; experimental study; genome-wide; insight; mRNA Export; optogenetics; transcription factor; vector; yeast genome

Project Summary Gene expression is regulated by transcription factors, chromatin structure and higher order organization. The positioning of genes within the nucleus and with respect to each other often correlates with their expression. The molecular mechanisms that control gene positioning within the nucleus are largely unknown. As a model for gene positioning, we have focused on the molecular mechanisms by which genes reposition from the nucleoplasm to the nuclear periphery upon activation in Saccharomyces cerevisiae. Targeting to the nuclear periphery involves a physical interaction with the nuclear pore complex (NPC) and is mediated by cis-acting DNA zip codes that are both necessary and sufficient to induce interaction with the NPC and localization at the nuclear periphery. Such zip codes also confer interchromosomal clustering of genes at the nuclear periphery. We have identified a number of transcription factors that bind to these zip codes and mediate targeting to the nuclear periphery. This suggests that controlling gene positioning is an unappreciated function of transcription factors and that cis-acting transcription factor binding sites represent a genetic means to control the spatial organization of the genome. The proposed studies will 1) determine the molecular mechanism by which the Gcn4 TF mediates targeting to the nuclear periphery and interchromosomal clustering, 2) comprehensively identify TFs and DNA binding proteins that impact gene positioning, and 3) test the hypothesis that TFs spatially and functionally compartmentalize the yeast genome.

项目摘要 基因表达受转录因子、染色质结构和高级有序度的调控 organization.基因在细胞核内的位置以及基因之间的相互关系通常与 他们的表情。控制基因在细胞核内定位的分子机制是 大部分未知。作为基因定位的模型，我们专注于分子机制， 哪些基因在酵母中激活后从核质重新定位到核周边 啤酒。靶向核外围涉及与核孔的物理相互作用 复合物（NPC），并通过顺式作用DNA邮政编码介导，这是必要和充分的 以诱导与NPC的相互作用和在核周边的定位。这样的邮政编码也 赋予核周边基因的染色体间聚类。我们已经确定了一些 这些转录因子结合这些邮政编码并介导靶向核周边。这 表明控制基因定位是转录因子的一种未被重视的功能， 顺式作用转录因子结合位点代表了控制空间组织的遗传手段 的基因组。 拟议的研究将1）确定Gcn 4 TF介导的分子机制 靶向核周边和染色体间聚类，2）全面鉴定TF， 影响基因定位的DNA结合蛋白，以及3）测试TF在空间上和 在功能上划分酵母基因组。