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Phenotypic robustness conferred by apparently redundant transcriptional enhancers


Genes include cis-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 of shavenbaby (svb, a transcript of the ovo locus), a gene encoding a transcription factor that directs development of Drosophila 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 the svb cDNA. Finally, removal of one copy of wingless, 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: The svb cis -regulatory region in D. melanogaster.
Figure 2: Effect of Df(X)svb 108 on the number of quaternary trichomes.
Figure 3: Rescue of the temperature-dependent trichome loss in the lateral patch by a Z::svb transgene.
Figure 4: Effect of Df(X)svb108 ; wg−/+ on the number of quaternary trichomes.

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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 the wg 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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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 to David 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. Nature 466, 490–493 (2010).

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