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Nature
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Phenotypic robustness conferred by apparently redundant transcriptional enhancers

Naturevolume 466, pages490–493 (2010)Cite this article

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Abstract

Genes includecis-regulatory regions that contain transcriptional enhancers. Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns1,2,3,4: primary enhancers located near the basal promoter and secondary, or ‘shadow’, enhancers located at more remote positions. It has been proposed that the seemingly redundant activity of primary and secondary enhancers contributes to phenotypic robustness1,5. We tested this hypothesis by generating a deficiency that removes two newly discovered enhancers ofshavenbaby (svb, a transcript of theovo locus), a gene encoding a transcription factor that directs development ofDrosophila larval trichomes6. At optimal temperatures for embryonic development, this deficiency causes minor defects in trichome patterning. In embryos that develop at both low and high extreme temperatures, however, absence of these secondary enhancers leads to extensive loss of trichomes. These temperature-dependent defects can be rescued by a transgene carrying a secondary enhancer driving transcription of thesvb cDNA. Finally, removal of one copy ofwingless, a gene required for normal trichome patterning7, causes a similar loss of trichomes only in flies lacking the secondary enhancers. These results support the hypothesis that secondary enhancers contribute to phenotypic robustness in the face of environmental and genetic variability.

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Figure 1:Thesvb cis-regulatory region inD. melanogaster.
Figure 2:Effect ofDf(X)svb108 on the number of quaternary trichomes.
Figure 3:Rescue of the temperature-dependent trichome loss in the lateral patch by aZ::svb transgene.
Figure 4:Effect ofDf(X)svb108 ;wg−/+ on the number of quaternary trichomes.

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Acknowledgements

We thank D. Chien and D. Erezyilmaz for assistance with early experiments, L. Kruglyak, S. Levin and S. Tavazoie for helpful comments on the manuscript, and E. Wieschaus for providing thewg mutant flies. This work was supported by The Pew Charitable Trusts Latin American Fellows Program in the Biomedical Sciences Fellowship to N.F., Agence Nationale de la Recherche (Blanc 2008, Netoshape) to F.P., and NIH (GM063622-06A1) and NSF (IOS-0640339) grants to D.L.S.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA,

    Nicolás Frankel, Diego Vargas, Shu Wang & David L. Stern

  2. Department of Biology, Bryn Mawr College, 101 N. Merion Ave, Bryn Mawr, Pennsylvania 19010, USA,

    Gregory K. Davis

  3. Université de Toulouse and Centre National de la Recherche Scientifique, Centre de Biologie du Développement, UMR5547, Toulouse, F-31062, France ,

    François Payre

Authors
  1. Nicolás Frankel

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  2. Gregory K. Davis

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  3. Diego Vargas

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  4. Shu Wang

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  5. François Payre

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  6. David L. Stern

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Contributions

N.F., G.K.D. and D.L.S. designed the experiments. N.F., G.K.D., D.V., S.W., F.P. and D.L.S. performed the experimental work. N.F. and D.L.S. wrote the manuscript. G.K.D. and F.P. commented on the manuscript at all stages.

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Correspondence toDavid L. Stern.

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The authors declare no competing financial interests.

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Frankel, N., Davis, G., Vargas, D.et al. Phenotypic robustness conferred by apparently redundant transcriptional enhancers.Nature466, 490–493 (2010). https://doi.org/10.1038/nature09158

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Editorial Summary

Back-up enhancers protect phenotype

Transcriptional enhancers are segments of regulatory DNA located some distance from the coding region of a gene. Sometimes, several of them can serve apparently redundant functions — driving the production of a gene's messenger RNA at the same stage and place in embryonic development. Frankelet al. now demonstrate inDrosophila that such 'redundant' enhancers (in this case, two enhancers of the embryo-patterning geneshavenbaby), by contributing higher overall levels of transcription, ensure robustness of phenotypes against both genetic and environmental perturbations; for example, mutations in other genes or temperature changes that would otherwise lead to aberrant development.

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