Beyond the Balance of Activator and Repressor

Cell differentiation during development is controlled by extracellular morphogens, which induce responding cells to differentiate into distinct cell fates based on the dose of morphogen they receive. Genes that specify the distinct cell fates are differentially responsive to morphogens, and the extracellular morphogen gradient is converted in responding cells to graded activity of transcription factors. In the case of Hedgehog, the gradient is converted to opposing gradients of transcriptional activator and repressor forms of the transcription factor Cubitus interruptus (Ci). It has been generally assumed that the balance between activator and repressor determines target gene responses within this gradient. However, new evidence shows that enhancers can respond selectively to the activator and repressor forms of Ci, and that this selectivity is determined by the affinity of Ci sites within the enhancers.