Abstract
The transforming growth factor β (TGF-β) family member Decapentaplegic (Dpp) is a key regulator of patterning and growth in Drosophila development. Previous studies have identified a short DNA motif called the silencer element (SE), which recruits a trimeric Smad complex and the repressor Schnurri to downregulate target enhancers upon Dpp signaling. We have now isolated the minimal enhancer of the dad gene and discovered a short motif we termed the activating element (AE). The AE is similar to the SE and recruits the Smad proteins via a conserved mechanism. However, the AE and SE differ at important nucleotide positions. As a consequence, the AE does not recruit Schnurri but rather integrates repressive input by the default repressor Brinker and activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA binding. The AE allows the identification of hitherto unknown direct Dpp targets and is functionally conserved in vertebrates.
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Acknowledgements
We are deeply thankful to B. Hartmann (University of Freiburg) for generously providing the flies transgenic for UAS-ShnVP16. Work in the lab of M.A. was supported by the Kantons Basel-Stadt and Basel-Land, by the Swiss National Science Foundation and by SystemsX.ch within the framework of the wingX RTD. Work in G.P.'s laboratory was supported by the German Research Foundation (SFB592) and the Excellence Initiative of the German Federal and State Governments (EXC294).
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A.W., E.C., E.E. and C.W. performed the experiments; A.T. and A.W. generated the bioinformatic data; A.W. and M.A. wrote the manuscript; M.A., G.P. and R.S. contributed to design and interpretation of the experiments and payed the bills.
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Supplementary Figures 1–7 and Supplementary Table 1 (PDF 1744 kb)
Supplementary Table 2
List of conserved AEs. (XLS 260 kb)
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Weiss, A., Charbonnier, E., Ellertsdóttir, E. et al. A conserved activation element in BMP signaling during Drosophila development. Nat Struct Mol Biol 17, 69–76 (2010). https://doi.org/10.1038/nsmb.1715
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DOI: https://doi.org/10.1038/nsmb.1715
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