Downstream Targets of Olig 2

Olig 2 的下游靶标

• 批准号: 7111895
• 负责人: SHWETAL MEHTA
• 金额: $ 4.88万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111895
• 关键词: brain; gene targeting; genes; genetics; glioma; multiple sclerosis; neoplasm /cancer; proteins; role; transcription factor

DESCRIPTION (provided by applicant): During development, a pair of basic helix-loop-helix transcription factor, Olig1 and Olig2 regulates fate choice decisions of neural progenitor cells to form neurons or oligodendrocytes. In the adult brain, these same two transcription factors appear to have functional roles in glial disease states such as multiple sclerosis and malignant glioma. Despite the crucial role of Olig genes in glial fate decisions, the molecular mechanism(s) by which Olig genes exert these important functions are largely unresolved. To this point, there has been no report of any direct downstream genetic target, which is either expressed or repressed by Olig proteins. The broad goal of this project is to identify direct downstream genetic targets of Olig2 specifically by achieving the following two aims: 1) a genome-wide screen of DNA regions associated with Olig2 in tumor cell lines and 2) gene expression profiling of genes regulated by Olig2 in presence of conditionally expressed Olig2 protein. In short run the target genes will reveal the biochemical function of Olig2 in transcription regulation. Eventually, these target genes might have practical overtones for targeted therapy of glioma or multiple sclerosis.

描述（申请人提供）：在发育过程中，一对碱性螺旋-环-螺旋转录因子Olig1和Olig2调节神经祖细胞形成神经元或少突胶质细胞的命运选择决定。在成人大脑中，这两种转录因子似乎在神经胶质疾病状态（如多发性硬化症和恶性神经胶质瘤）中发挥功能作用。尽管 Olig 基因在神经胶质细胞命运决定中发挥着至关重要的作用，但 Olig 基因发挥这些重要功能的分子机制在很大程度上尚未解决。到目前为止，还没有任何直接下游遗传靶标的报道，该靶标要么被 Olig 蛋白表达，要么被抑制。该项目的总体目标是通过实现以下两个目标来确定 Olig2 的直接下游遗传靶标：1）对肿瘤细胞系中与 Olig2 相关的 DNA 区域进行全基因组筛选，2）对受 Olig2 调控的基因进行基因表达谱分析。 Olig2 存在条件表达的 Olig2 蛋白。短期内，目标基因将揭示Olig2在转录调控中的生化功能。最终，这些靶基因可能对神经胶质瘤或多发性硬化症的靶向治疗具有实际意义。