Transcriptional Silencers in Drosophila Serve a Dual Role as Transcriptional Enhancers in Alternate Cellular Contexts

UMMS Affiliation

Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Bioinformatics | Cell and Developmental Biology | Genetics and Genomics | Systems Biology


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 10(4)-10(5) in humans.


enhancers, silencers, cis-regulatory elements, transcriptional regulation, repression, promoter looping

DOI of Published Version



Mol Cell. 2020 Jan 16;77(2):324-337.e8. doi: 10.1016/j.molcel.2019.10.004. Epub 2019 Nov 5. Link to article on publisher's site

Journal/Book/Conference Title

Molecular cell

Related Resources

Link to Article in PubMed

PubMed ID