The Mediator complex in gene regulation of the ß-globin locus: Analysis and characterization of Mediator subunit Med1/TRAP220 conditional knock-out mice

β-珠蛋白位点基因调控的介体复合物：介体亚基 Med1/TRAP220 条件敲除小鼠的分析和表征

• 批准号: 69035882
• 负责人: Professor Dr. Tilman Borggrefe
• 金额: --
• 依托单位: Biochemisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/69035882?language=en
• 关键词: Mediator; complex; gene; regulation; globin

The Mediator complex forms the bridge between transcriptional activators and the RNA polymerase II. Med1/TRAP220 is a key component of Mediator originally found to associate with nuclear hormone receptors. Med1 knockout mice die in embryonic development at day 11.5 days post coitum. So far, we could demonstrate that Med1 interacts physically with the erythroid master regulator GATA-1, is found at GATA-1 target genes and is required for GATA-1 dependent transcriptional activation. Thus, we concluded that Mediator subunit Med1 acts as a pivotal coactivator for GATA-1 in erythroid development (Stumpf et al., 2006). Now, we want to use conditional Med1 knock-out mice in order 1) to analyze the phenotype of Medl-deficient mice in adult erythropoiesis and 2) to dissect the molecular mechanism of transcriptional activation at the ßglobin locus, the best-studied gene locus for gene activation in higher eukaryotes. The overall goal of the proposed project is to understand the role of Mediator in gene activation.

介体复合物形成转录激活因子和RNA聚合酶II之间的桥梁。Med 1/TRAP 220是最初发现与核激素受体相关的Mediator的关键组分。Med 1基因敲除小鼠在胚胎发育中于交配后11.5天死亡。到目前为止，我们可以证明Med 1与红细胞主调节因子加塔-1物理相互作用，发现在加塔-1靶基因中，并且是加塔-1依赖性转录激活所必需的。因此，我们得出结论，中介子亚基Med 1在红系发育中充当加塔-1的关键共活化剂（Stumpf等，2006年）。现在，我们希望使用条件性Med 1敲除小鼠，以便1）分析Med 1缺陷小鼠在成年红细胞生成中的表型，以及2）剖析β珠蛋白基因座处转录激活的分子机制，β珠蛋白基因座是高等真核生物中基因激活的最佳研究基因座。该项目的总体目标是了解Mediator在基因激活中的作用。