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Cited by 48Genomics and Chromatin DynamicsEstrogen and related hormone effectsChromatin Remodeling and Cancer

Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci

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Jubb, Alasdair W., Boyle, Shelagh, Hume, David A., Bickmore, Wendy A.·2017·Cell Reports
DOI 10.1016/j.celrep.2017.11.053PMC PMC5745231
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Abstract

Glucocorticoids act by binding to the glucocorticoid receptor (GR), which binds to specific motifs within enhancers of target genes to activate transcription. Previous studies have suggested that GRs can promote interactions between gene promoters and distal elements within target loci. In contrast, we demonstrate here that glucocorticoid addition to mouse bone-marrow-derived macrophages produces very rapid chromatin unfolding detectable by fluorescence in situ hybridization (FISH) at loci associated with GR binding. Rapid chromatin decompaction was generally not dependent on transcription at those loci that are known to be inducible in both mouse and human macrophages and was sustained for up to 5 days following ligand removal. Chromatin decompaction was not dependent upon persistent GR binding, which decayed fully after 24 hr. We suggest that sustained large-scale chromatin reorganization forms an important part of the response to glucocorticoid and might contribute to glucocorticoid sensitivity and resistance.

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  • Transcription at stimulus-response genes was shown to disrupt chromatin loops, potentially through destabilising cohesin association with the chromatin fibre by RNAP machinery.

    “For example, transcription at stimulus–response genes was shown to disrupt chromatin loops [387, 388], potentially through destabilising cohesin association with the chromatin fibre by RNAP machinery [388].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [387]

    The Results report chromatin decompaction at glucocorticoid-responsive loci, but the Discussion says dissolution of preformed loops cannot be excluded—not that transcription was shown to disrupt loops. The Results and Discussion also say decompaction can occur without transcription. Our copy does not identify destabilisation of cohesin by RNAP machinery as a mechanism (searched: cohesin). (LLM, conf=0.88)

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Authors
Jubb, A. W., Boyle, S., Hume, D. A., & Bickmore, W. A.
Affiliations
  • Roslin Institute (GB)
  • Institute of Genetics and Cancer (GB)
  • Translational Research Institute (AU)
Corresponding author
  • Hume, David A.
  • Bickmore, Wendy A.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2017-12
Volume
21
Issue
11
Pages
3022-3031
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2017.11.053
PMC
PMC5745231
OpenAlex
W2772149037
Cited by
48
References
8
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 7 · 2018: 8
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (097481/Z/11/Z, U127527202)
  • UK Medical Research Council
  • BBSRC
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
glucocorticoid receptor, chromatin decompaction, glucocorticoid signaling, macrophages, enhancer-promoter interactions, transcriptional regulation, glucocorticoid resistance, glucocorticoid sensitivity, chromatin reorganization, ligand binding
MeSH terms
Kruppel-Like Factor 4, Animals, Binding Sites, Chromatin, Dexamethasone, DNA-Binding Proteins, Gene Expression Regulation, Humans, Kinetics, Macrophages, Male, Mice, Inbred C57BL, Promoter Regions, Genetic, Protein Binding, Receptors, Glucocorticoid, Transcription Factors, Signal Transduction, Proto-Oncogene Proteins c-fos, In Situ Hybridization, Fluorescence, Chromatin Assembly and Disassembly, Mice, Kruppel-Like Transcription Factors, Nuclear Receptor Coactivators, Primary Cell Culture

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