Downstream Targets of Olig 2

描述（由申请人提供）：在发育过程中，一对碱性螺旋-环-螺旋转录因子Olig 1和Olig 2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和恶性神经胶质瘤中具有功能性作用。尽管Olig基因在胶质细胞命运决定中起着关键作用，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点的报道，其被Olig蛋白表达或抑制。该项目的广泛目标是通过实现以下两个目标来特异性地鉴定Olig 2的直接下游遗传靶标：1）肿瘤细胞系中与Olig 2相关的DNA区域的全基因组筛选和2）在条件表达的Olig 2蛋白存在下由Olig 2调节的基因的基因表达谱。在短期内，目标基因将揭示Olig 2在转录调控中的生化功能。最终，这些靶基因可能对胶质瘤或多发性硬化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.