DNA topoisomerases are thought to facilitate transcription by removing excess topological strain induced by the tracking of the polymerase. A study in Saccharomyces cerevisiae deficient for topoisomerases I and II has now suggested that in vivo these enzymes are also involved in gene activation. Genes particularly affected in topoisomerase mutants have features associated with highly regulated transcription, such as a TATA box, which is indicative of a repressible and/or inducible mode of transcription. For the gene PHO5, the authors showed that topoisomerases are required for transcription factor binding.