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PreprintCited by 32Genomics and Chromatin DynamicsGene Regulatory Network AnalysisDiffusion and Search Dynamics

Mechanisms of transcription control by distal enhancers from high-resolution single-gene imaging

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Cheng, Lingling, De, Chayan, Li, Jieru, Pertsinidis, Alexandros·2023·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2023.03.19.533190PMC PMC10055225
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Abstract

How distal enhancers physically control promoters over large genomic distances, to enable cell-type specific gene expression, remains obscure. Using single-gene super-resolution imaging and acute targeted perturbations, we define physical parameters of enhancer-promoter communication and elucidate processes that underlie target gene activation. Productive enhancer-promoter encounters happen at 3D distances δ200 nm - a spatial scale corresponding to unexpected enhancer-associated clusters of general transcription factor (GTF) components of the Pol II machinery. Distal activation is achieved by increasing transcriptional bursting frequency, a process facilitated by embedding a promoter into such GTF clusters and by accelerating an underlying multi-step cascade comprising early phases in the Pol II transcription cycle. These findings help clarify molecular/biochemical signals involved in long-range activation and their means of transmission from enhancer to promoter.

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  • 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 [55]

    In “A multi-step cascade underlies the initiation of transcriptional bursts” (page unavailable), the paper says enhancers mostly control burst frequency. But it describes promoter control of burst size as a proposed view, then reports that perturbing promoter-associated transcription machinery predominantly changed burst frequency while burst duration remained unchanged. It therefore does not establish that promoter properties determine cycle duration. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 32

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Cited by

Sorted by citations

Authors
Cheng, L., De, C., Li, J., & Pertsinidis, A.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Pertsinidis, Alexandros
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2023-03-21
DOI
10.1101/2023.03.19.533190
PMC
PMC10055225
OpenAlex
W4328124774
Cited by
32
References
4
Citations by year
2026: 4 · 2025: 14 · 2024: 10 · 2023: 4
Type
posted content
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Howard Hughes Medical Institute (P30 CA008748)
  • Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748)
  • University of Dundee
  • Starr Foundation (P30CA008748)
  • New York State Stem Cell Science (C32599GG)
  • National Institutes of Health (CA008748)
  • Medical Research Council
  • National Cancer Institute (CA008748, P30CA008748)
  • National Institute of General Medical Sciences (R21GM134342, R01GM135545, R01GM144508)
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 › Diffusion and Search Dynamics
Keywords
distal enhancers, enhancer-promoter interactions, long-range gene regulation, transcriptional bursting, general transcription factors, RNA polymerase II, super-resolution imaging, cell type-specific gene expression, transcriptional cascade

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