Credit: IMAGE100

Many developmental genes contain multiple enhancers that drive apparently redundant patterns of transcription, but what are the functions of these various regulatory elements? A new study in Drosophila species indicates that secondary, 'shadow' enhancers, which are distant from promoter regions, confer phenotypic robustness to environmental and genetic perturbations.

Frankel, Stern and colleagues identified two secondary enhancers (Z and DG2) that lie upstream of three known enhancers in the shavenbaby (svb) gene, which encodes a transcription factor. To examine the function of these new enhancers, they generated a deficiency strain in which both enhancers were removed. First-instar larvae from the deficiency strain that developed at an optimal temperature showed only subtle trichome (hair) abnormalities. There was a clear overlap between the expression patterns driven by Z and DG2 and the previously identified svb enhancers, suggesting that the mild phenotype of the deficiency larvae might be because the primary enhancers drive sufficient levels of svb transcription under optimal developmental conditions.

One possibility is that secondary enhancers contribute to phenotypic robustness. The authors tested this hypothesis: deficiency larvae that developed at extreme temperatures produced significantly fewer trichomes than control embryos that developed at intermediate temperatures. The loss of trichomes in the deficiency strain could be rescued by a transgene carrying the svb cDNA under the control of the Z enhancer, further supporting the idea that these enhancers contribute to robustness against environmental perturbations.

Do the svb shadow enhancers also buffer against genetic variability? The authors crossed the deficiency strain into a background heterozygous for a null allele of wingless, a gene required for normal trichome development. This resulted in reduced trichome number compared with control larvae. The authors suggest that apparently redundant enhancers in other developmental genes could confer similar functions and that secondary enhancers might be maintained by selection for robustness against environmental and genetic variability. Uncovering the molecular mechanisms that contribute to this developmental buffering will be the next step forward.