Cited by 721Genomics and Chromatin DynamicsGene Regulatory Network AnalysisDevelopmental Biology and Gene Regulation

Enhancer Control of Transcriptional Bursting

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Fukaya, Takashi, Lim, Bomyi, Levine, Michael·2016·Cell

Abstract

Transcription is episodic, consisting of a series of discontinuous bursts. Using live-imaging methods and quantitative analysis, we examine transcriptional bursting in living Drosophila embryos. Different developmental enhancers positioned downstream of synthetic reporter genes produce transcriptional bursts with similar amplitudes and duration but generate very different bursting frequencies, with strong enhancers producing more bursts than weak enhancers. Insertion of an insulator reduces the number of bursts and the corresponding level of gene expression, suggesting that enhancer regulation of bursting frequency is a key parameter of gene control in development. We also show that linked reporter genes exhibit coordinated bursting profiles when regulated by a shared enhancer, challenging conventional models of enhancer-promoter looping.

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Crossref · 10.1016/j.cell.2016.05.025

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  • Enhancers increase the frequency of transcriptional bursts without significantly affecting their amplitude and duration.

    “Evidence from live imaging and single-cell transcriptomics indicates that enhancers increase the frequency of transcriptional bursts without significantly affecting their amplitude and duration [310, 505, 516].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [310]

    The Abstract and Results (Differential bursting frequencies) report that stronger enhancers generally produce more bursts with similar amplitudes and durations. However, the Results identify a significant reduction in burst amplitude for the Kr CD2 enhancer, so the claim that amplitude is not significantly affected needs that exception. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Enhancers increase the frequency of transcription cycles, while their duration is determined by the properties of the promoter.

    “Existing experimental data suggest that enhancers increase the frequency of cycles, while their duration is determined by the properties of the promoter [53,54,55,56].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [53]

    The Abstract and Discussion (Regulation of bursting frequencies; page unavailable) report that stronger enhancers produce more bursts, while bursts from different enhancers have similar durations. The Results (Differential bursting frequencies; page unavailable) compare promoters but report effects on burst frequency and amplitude, not that promoter properties determine burst duration. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Evidence from live imaging shows that an enhancer located in-between two reporter genes can initiate simultaneous transcriptional bursting from both gene promoters.

    “evidence from live imaging shows that an enhancer located in-between two reporter genes can initiate simultaneous transcriptional bursting from both gene promoters [310].”
  • Physical contacts between enhancers and promoters are often highly dynamic.

    “Evidence from live-imaging studies at candidate loci suggests that physical contacts between enhancers and promoters are often highly dynamic [310, 311, 448].”
  • An enhancer can target all genes within an insulated chromatin structure in Drosophila.

    “recent evidence in Drosophila suggests that an enhancer can target all genes within an insulated chromatin structure (Fukaya et al., 2016)”

    From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Fukaya et al., 2016

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Authors
Fukaya, T., Lim, B., & Levine, M.
Affiliations
Princeton University (US)
Corresponding author
Levine, Michael
Venue
Cell
Publisher
Elsevier BV
Published
2016-07
Volume
166
Issue
2
Pages
358-368
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2411956266
Cited by
721
References
49
Citations by year
2026: 38 · 2025: 73 · 2024: 69 · 2023: 65 · 2022: 72 · 2021: 97 · 2020: 97 · 2019: 88 · 2018: 67 · 2017: 44 · 2016: 11
FWCI
36.37
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Drug Abuse (U01DA047730)
  • National Institute of General Medical Sciences (R37GM046638, R01GM034431, R01GM046638)
  • National Institute of Biomedical Imaging and Bioengineering (U01EB021239)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
transcriptional bursting, enhancer regulation, Drosophila embryo, insulator proteins, enhancer-promoter looping, gene expression regulation, developmental enhancers
MeSH terms
Animals, Chromosomes, Drosophila melanogaster, Embryo, Nonmammalian, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Male, Promoter Regions, Genetic, Transcription, Genetic, Transcriptional Activation, Genes, Reporter, Insulator Elements, Green Fluorescent Proteins

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