A revised model for promoter competition based on multi-way chromatin interactions at the α-globin locus
Open accessPublished version of a preprint
Abstract
Specific communication between gene promoters and enhancers is critical for accurate regulation of gene expression. However, it remains unclear how specific interactions between multiple regulatory elements contained within a single chromatin domain are coordinated. Recent technological advances which can detect multi-way chromatin interactions at single alleles can provide insights into how multiple regulatory elements cooperate or compete for transcriptional activation. Here, we use such an approach to investigate how interactions of the α-globin enhancers are distributed between multiple promoters in a mouse model in which the α-globin domain is extended to include several additional genes. Our data show that gene promoters do not form mutually exclusive interactions with enhancers, but all interact simultaneously in a single complex. These findings suggest that promoters do not structurally compete for interactions with enhancers, but form a regulatory hub structure, which is consistent with recent models of transcriptional activation occurring in non-membrane bound nuclear compartments.
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Tri-C and MC-4C provided evidence for higher-order hubs containing three and more regulatory elements in the α- and β-globin loci.
“Both technologies, applied in the α- and β- globin loci respectively, provided evidence for higher-order hubs, containing three and more regulatory elements [499, 485].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [499]
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References 39 · Cited by 80
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- Authors
- Oudelaar, A. M., Harrold, C. L., Hanssen, L. L. P., Telenius, J. M., Higgs, D. R., & Hughes, J. R.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Hughes, Jim R.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-11-27
- Volume
- 10
- Issue
- 1
- Pages
- 5412-5412
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6881440
- OpenAlex
- W2989914470
- Cited by
- 80
- References
- 39
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 16 · 2021: 11 · 2020: 12 · 2019: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- RCUK | Medical Research Council
- Wellcome Trust
- 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 › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- promoter competition, alpha-globin locus, enhancer-promoter interactions, transcriptional activation, regulatory hubs, chromatin domains, nuclear compartments
- MeSH terms
- Animals, Binding Sites, Chromatin, Enhancer Elements, Genetic, Female, Membrane Proteins, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Genetic, Promoter Regions, Genetic, alpha-Globins, Genetic Loci
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