The complex processes of eukaryotic gene expression are controlled by a relatively small number of transcription factors whose activities are modulated by a diverse set of regulatory mechanisms. A recent paper describes the molecular basis for one such mechanism in which the Pit-1 transcription factor activates or represses transcription depending on the sequence of the DNA to which it binds. The mechanism by which the binding-site sequence regulates the activity of Pit-1 is discussed in relation to that of other transcription factors.