The polycomb group gene BMIl is a target gene of E2F-1: role of Bmi1 in E2F-controlled genetic programs and mode of functional interaction with E2F-1

多梳组基因BMIl是E2F-1的靶基因：Bmi1在E2F控制的遗传程序中的作用以及与E2F-1的功能相互作用模式

• 批准号: 5422440
• 负责人: Privatdozent Dr. Werner Lutz
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5422440?language=en
• 关键词: polycomb; group; gene; BMIl; target

E2F transcription factors activate the MYCN gene in a subset of aggressive neuroblastomas. In a search for additional oncogenic target genes of E2F, we have generated neuroblastoma cells that express the 4-hydroxy-tamoxifen regulated E2F-1-ER fusion protein. cDNA-microarray analysis, quantitative RT-PCR, and chromatin immunoprecipitation identified the polycomb group protein BMI1 as a direct target gene of E2F-1 in both human neuroblastoma cells and rat fibroblasts, consistent with the presence of a conserv ed E2F binding site in the BMI1 promoter. The regulatory interaction between E2F-1 and BMI1 raises several questions: 1. Is the activation of BMI1 necessary for the induction of S-phase or apoptosis by E2F-1, or is BMI1 part of a distinct cellular program triggered by E2F-1? 2. How is Bmi1 mechanistically integrated into the response of cells to activated E2F-1? These questions will be addressed with a combination of gain and loss of function approaches and global gene expression analyses.

E2F转录因子激活侵袭性神经母细胞瘤的MYCN基因。为了寻找E2F的其他致癌靶基因，我们已经产生了表达4-羟基他莫昔芬调节的E2F-1-ER融合蛋白的神经母细胞瘤细胞。基因芯片分析、定量RT-PCR和染色质免疫沉淀证实BMI1是E2F-1在人神经母细胞瘤细胞和大鼠成纤维细胞中的直接靶基因，这与BMI1启动子中存在保守的E2F结合位点是一致的。E2F-1和Bmi 1之间的调控相互作用提出了几个问题：1.Bmi 1的激活是诱导E2F-1诱导S期或细胞凋亡所必需的，还是Bmi 1是由E2F-1触发的独特细胞程序的一部分？2.Bmi1是如何机械地整合到细胞对激活的E2F-1的反应中的？这些问题将通过功能获得和功能丧失方法以及全球基因表达分析相结合来解决。