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Cited by 363Genomics and Chromatin DynamicsCRISPR and Genetic EngineeringNuclear Structure and Function

Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements

Open access
Gu, Bo, Swigut, Tomek, Spencley, Andrew, Bauer, Matthew R., Chung, Mingyu, Meyer, Tobias, Wysocka, Joanna·2018·Science
DOI 10.1126/science.aao3136PMC PMC6590518
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Abstract

To achieve guide RNA (gRNA) multiplexing and an efficient delivery of tens of distinct gRNAs into single cells, we developed a molecular assembly strategy termed chimeric array of gRNA oligonucleotides (CARGO). We coupled CARGO with dCas9 (catalytically dead Cas9) imaging to quantitatively measure the movement of enhancers and promoters that undergo differentiation-associated activity changes in live embryonic stem cells. Whereas all examined functional elements exhibited subdiffusive behavior, their relative mobility increased concurrently with transcriptional activation. Furthermore, acute perturbation of RNA polymerase II activity can reverse these activity-linked increases in loci mobility. Through quantitative CARGO-dCas9 imaging, we provide direct measurements of cis-regulatory element dynamics in living cells and distinct cellular and activity states and uncover an intrinsic connection between cis-regulatory element mobility and transcription.

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Crossref · 10.1126/science.aao3136

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  • Other studies have found enhancer mobility, rather than proximity per se, to be a key determinant of activation.

    “Other studies have found enhancer mobility, rather than proximity per se, to be a key determinant of activation154.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [154]

    The paper reports greater Fgf5 enhancer mobility in actively transcribing cells and links mobility to transcriptional activity (Abstract; page unavailable). But it does not establish mobility, rather than proximity, as a key determinant of activation. Its proposed mechanism is tentative: mobility may increase enhancer–promoter encounters and reinforce expression after transcription begins. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Some established mechanisms of enhancer-gene interaction, such as high physical mobility or weak interaction networks, may not translate well to an MPRA context.

    “Also, some established mechanisms of enhancer–gene interaction, such as high physical mobility154 or weak interaction networks218, may not translate well to an MPRA context.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [154]

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Cited by

Sorted by citations

Authors
Gu, B., Swigut, T., Spencley, A., Bauer, M. R., Chung, M., Meyer, T., & Wysocka, J.
Affiliations
  • Stanford Medicine (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Wysocka, Joanna
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2018-03-02
Volume
359
Issue
6379
Pages
1050-1055
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aao3136
PMC
PMC6590518
OpenAlex
W2785060777
Cited by
363
References
1
Citations by year
2026: 21 · 2025: 41 · 2024: 41 · 2023: 43 · 2022: 44 · 2021: 44 · 2020: 52 · 2019: 48 · 2018: 28
FWCI
15.30
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (GM112720)
  • Howard Hughes Medical Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
cis-regulatory elements, nuclear mobility, enhancers, promoter, transcription, RNA polymerase II, subdiffusion, embryonic stem cells, cell differentiation, live-cell imaging
MeSH terms
Single Molecule Imaging, CRISPR-Associated Protein 9, RNA, Guide, CRISPR-Cas Systems, Animals, Bacterial Proteins, Cell Line, Cell Nucleus, Endonucleases, Regulatory Sequences, Nucleic Acid, RNA Polymerase II, Transcription, Genetic, Transcriptional Activation, RNA, Guide, Kinetoplastida, Oligonucleotide Array Sequence Analysis, Mice, Single-Cell Analysis

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