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. Almost all of the transcriptional silencers that 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 forms 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 104–105 in humans. Display omitted •Silencers are bifunctional and can act as enhancers in other cellular contexts•A subset of silencers forms long-range contacts to promoters•Deletion of a silencer by genome editing caused derepression of its target gene•Results suggest that thousands of bifunctional elements in flies remain to be discovered Gisselbrecht et al. performed a screen in developing Drosophila embryos for genomic sequences that can act as transcriptional silencers. They report that nearly all silencers are enhancers in other tissues or at other developmental stages. Their silencers fall into two classes, one of which forms physical chromosomal contacts with promoters.