DNA topoisomerases are enzymes, which function to relieve torsional stress in the DNA helix by introducing transient breaks into the DNA molecule. By use of Saccharomyces cerevisiae and microarray technology we have previously shown that topoisomerases are required for the activation of chromatin regulated genes. A further study of the PHO5 gene belonging to this gene class demonstrated a lack of binding of the transcription factor Pho4 to the PHO5 promoter in the absence of topoisomerases, most likely due to changes in the overall superhelical state of the promoter. The GAL genes also require topoisomerases for optimal activation, but in contrast to the PHO5 gene, topoisomerases are not required for chromatin remodeling of the GAL1/10 promoter region, indicating a different role of the enzymes. We are currently performing a detailed investigation of the GAL genes to elucidate the precise role of topoisomerases during the activation process, and the obtained results will be presented.