Downstream Targets of Olig 2

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--寡核苷酸1和寡核苷酸2调节神经前体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，这两个相同的转录因子似乎在多发性硬化症和恶性胶质瘤等神经胶质疾病状态中发挥功能作用。尽管Olig基因在决定神经胶质命运中起着至关重要的作用，但Olig基因发挥这些重要功能的分子机制(S)在很大程度上还没有解决。到目前为止，还没有关于由Olig蛋白表达或抑制的任何直接下游遗传靶点的报道。这个项目的主要目标是通过实现以下两个目标来明确Otl2的直接下游遗传靶点：1)在肿瘤细胞系中筛选与Olob2相关的DNA区域；2)在条件表达的Otl2蛋白存在的情况下，对Olob2调控的基因进行基因表达谱分析。在短期内，靶基因将揭示Orig2在转录调控中的生化功能。最终，这些靶基因可能会对胶质瘤或多发性硬化症的靶向治疗产生实际影响。

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.