ONLINE COVER This week features a Research Article (see also the accompanying Perspective) that uncovers the mechanisms controlling gene expression in response to gradients of Hedgehog ligands, one of which is the counterintuitive effect of the affinity of transcription factor binding sites. The image shows a Drosophila wing imaginal disc in which expression of a Hedgehog target gene is driven by a wild-type enhancer with low-affinity transcription factor binding sites (yellow) or an altered enhancer with high-affinity transcription factor binding sites (blue). [Image: David S. Parker, University of Michigan Medical School]

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