Suboptimization of developmental enhancers

For gene enhancers, less is more Weak enhancer sequences provide just the right amount of gene activity. Farley et al. systematically examined millions of synthetic variants of the Otx enhancer, a motif needed for gene expression in the nervous system of the sea squirt Ciona. Proper gene activity resulted when there were imperfect matches to the motif showing strongest enhancer binding and gene activation. When “optimal” motifs were incorporated, ectopic expression ensued, with aberrant gene activation outside the nervous system. Science , this issue p. 325