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Cited by 146Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

High-throughput functional comparison of promoter and enhancer activities

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Nguyen, Thomas A., Jones, Richard D., Snavely, Andrew R., Pfenning, Andreas R., Kirchner, Rory, Hemberg, Martin, Gray, Jesse M.·2016·Genome Research
DOI 10.1101/gr.204834.116PMC PMC4971761
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Abstract

Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons. We focused on genomic loci bound by the neuronal activity-regulated coactivator CREBBP, and we measured enhancer and promoter activities both before and after neuronal activation. We find that the same sequences typically encode both enhancer and promoter activities. However, gene promoters generate more promoter activity than distal enhancers, despite generating similar enhancer activity. Surprisingly, the greater promoter activity of gene promoters is not due to conventional core promoter elements or splicing signals. Instead, we find that particular transcription factor binding motifs are intrinsically biased toward the generation of promoter activity, whereas others are not. Although the specific biases we observe may be dependent on experimental or cellular context, our results suggest that gene promoters are distinguished from distal enhancers by specific complements of transcriptional activators.

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  • Certain promoters, termed epromoters, can also function as enhancers.

    “Finally, evidence from multiple sources including reporter assays [169, 175, 239, 240], CRISPR [240–242], chromatin mapping [243, 244] and population genetics analysis [207, 245] suggests that certain promoters, termed ‘epromoters’, can also function as enhancers (reviewed in [246]).”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [175]

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Cited by

Sorted by citations

Authors
Nguyen, T. A., Jones, R. D., Snavely, A. R., Pfenning, A. R., Kirchner, R., Hemberg, M., & Gray, J. M.
Affiliations
  • Harvard University (US)
  • MIT Computer Science and Artificial Intelligence Laboratory (US)
  • Wellcome Sanger Institute (GB)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2016-06-16
Volume
26
Issue
8
Pages
1023-1033
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.204834.116
PMC
PMC4971761
OpenAlex
W2424483111
Cited by
146
References
11
Citations by year
2026: 10 · 2025: 15 · 2024: 17 · 2023: 11 · 2022: 11 · 2021: 15 · 2020: 15 · 2019: 15 · 2018: 20 · 2017: 12 · 2016: 5
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01 MH101528-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
promoter activity, enhancer activity, CREB-binding protein, transcription factor binding motifs, transcriptional activator, core promoter elements, splicing signals, mouse neurons, neuronal activation, high-throughput functional genomics
MeSH terms
Animals, Binding Sites, Chromatin, DNA-Binding Proteins, Enhancer Elements, Genetic, Neurons, Promoter Regions, Genetic, Protein Binding, Transcription, Genetic, Sequence Analysis, DNA, CREB-Binding Protein, Mice

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