Transcriptional silencers in Drosophila serve a dual role as transcriptional enhancers in alternate cellular contexts. Gisselbrecht et al.
A major challenge in biology is to understand how complex gene expression patterns are encoded in the genome. While transcriptional enhancers have been studied extensively, few transcriptional silencers have been identified and they remain poorly understood. Here we used a novel strategy to screen hundreds of sequences for tissue-specific silencer activity in whole Drosophila embryos. Strikingly, almost all transcriptional silencers we identified were also active enhancers in other cellular contexts. These elements are bound by more transcription factors than non-silencers. A subset of these silencers form long range contacts with promoters. Deletion of a silencer caused derepression of its target gene. Our results challenge the common practice of treating enhancers and silencers as separate classes of regulatory elements and suggest the possibility that thousands or more bifunctional CRMs remain to be discovered in Drosophila and 10^4-10^5 in human. This dataset contains the raw imaging data (fluorescence photomicrographs of Drosophila embryos) used (after cropping, rotating, and resizing) to produce the figures in this paper. .zvi and .czi files can be opened with ZEN lite software, which is a free download at: https://www.zeiss.com/microscopy/us/products/microscope-software/zen-lite.html