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Cited by 128Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

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

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Gisselbrecht, Stephen S., Palagi, Alexandre, Kurland, Jesse V., Rogers, Julia M., Ozadam, Hakan, Zhan, Ye, Dekker, Job, Bulyk, Martha L.·2020·Molecular Cell
DOI 10.1016/j.molcel.2019.10.004PMC PMC6980774
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Abstract

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.

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  • Some enhancers are marked with H3K27me3 alone and are considered to be Polycomb-repressed.

    “Finally, some enhancers are marked with H3K27me3 alone and are considered to be “Polycomb-repressed” [139–141].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [140]

    The Results section on element selection describes H3K27me3 as a repressive mark at candidate regulatory elements, including elements that may act as enhancers in another cell type. It does not establish that those enhancers carry H3K27me3 alone or classify them as Polycomb-repressed. In the Results section on validated silencers, only 4 of 29 overlapped Polycomb response elements. (LLM, conf=0.84)

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Authors
Gisselbrecht, S. S., Palagi, A., Kurland, J. V., Rogers, J. M., Ozadam, H., Zhan, Y., Dekker, J., & Bulyk, M. L.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of Massachusetts Chan Medical School (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Bulyk, Martha L.
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2020-01
Volume
77
Issue
2
Pages
324-337.e8
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2019.10.004
PMC
PMC6980774
OpenAlex
W2984395420
Cited by
128
References
6
Citations by year
2026: 6 · 2025: 22 · 2024: 27 · 2023: 14 · 2022: 26 · 2021: 23 · 2020: 9 · 2019: 1
FWCI
4.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship@UMassChan (submittedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
transcriptional silencer, enhancers, Drosophila, enhancer silencing, cellular context, enhancer function, chromatin regulation
MeSH terms
Animals, Drosophila, Enhancer Elements, Genetic, Male, Transcription, Genetic, Animals, Genetically Modified, Silencer Elements, Transcriptional

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