FRA-2 is involved in cellular differentiation and is also upregulated in response to ischemic injury to the brain. To shed light on the function of this transcription factor, a novel microarray analysis was utilized to identify FRA-2-dependent gene expression increased in the hypoxic response. Genes were identified that were upregulated by exposure of neuronally differentiated PC12 cells to hypoxia. Using a dominant negative construct to block FRA-2, a second subset of genes that were FRA-2 dependent was found. Cross comparison then allowed isolation of a list of genes that were induced in response to hypoxia in a FRA-2-dependent manner. These data suggest that FRA-2 is involved in the transcriptional control of neuroprotective genes and in the switch from aerobic to anaerobic metabolism.