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.
|Mehta, Shwetal; Huillard, Emmanuelle; Kesari, Santosh et al. (2011) The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell 19:359-71|
|Sun, Yu; Meijer, Dimphna H; Alberta, John A et al. (2011) Phosphorylation state of Olig2 regulates proliferation of neural progenitors. Neuron 69:906-17|