Downstream Targets of Olig 2

描述（申请人提供）：在发育过程中，一对基本的螺旋-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策。在成人大脑中，这两种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oliggenes在胶质细胞命运决定中起着至关重要的作用，但oliggenes发挥这些重要功能的分子机制在很大程度上仍未得到解决。到目前为止，还没有任何直接的下游遗传靶点的报道，这些靶点要么被oligo蛋白表达，要么被oligo蛋白抑制。该项目的总体目标是通过实现以下两个目标来确定Olig2的直接下游遗传靶点：1)肿瘤细胞系中与Olig2相关的DNA区域的全基因组筛选；2)在有条件表达的Olig2蛋白存在的情况下，对Olig2调控的基因进行基因表达谱分析。短期内靶基因将揭示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。

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.