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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
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Abstract
The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new chromosome conformation capture (3C) approach, to characterize concurrent chromatin interactions at individual alleles. Analysis by Tri-C identifies heterogeneous patterns of single-allele interactions between CTCF boundary elements, indicating that the formation of chromatin domains likely results from a dynamic process. Within these domains, we observe specific higher-order structures that involve simultaneous interactions between multiple enhancers and promoters. Such regulatory hubs provide a structural basis for understanding how multiple cis-regulatory elements act together to establish robust regulation of gene expression.
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“in addition to multiple enhancers, hubs detected by these techniques sometimes contain multiple promoters, corroborating the evidence for promoter-promoter contacts from the conventional 3C-derived methods [453, 498].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [498]
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“In the last decade, proximity ligation methods have played an important role in identifying these key interactions, such as promoter and enhancer associations (Kempfer and Pombo, 2020; Oudelaar et al., 2018; Quinodoz et al., 2018).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Oudelaar et al., 2018
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Metadata
- Authors
- Oudelaar, A. M., Davies, J. O. J., Hanssen, L. L. P., Telenius, J. M., Schwessinger, R., Liu, Y., Brown, J. M., Downes, D. J., Chiariello, A. M., Bianco, S., Nicodemi, M., Buckle, V. J., Dekker, J., Higgs, D. R., & Hughes, J. R.
- Affiliations
- University of Oxford (GB)
- University of Massachusetts Chan Medical School (US)
- Istituto Nazionale di Fisica Nucleare (IT)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hughes, Jim R.
- ORCID
- Venue
- Nature Genetics
- Published
- 2018-10-29
- Volume
- 50
- Issue
- 12
- Pages
- 1744-1751
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC6265079
- OpenAlex
- W2897970825
- Cited by
- 196
- References
- 55
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 23 · 2023: 24 · 2022: 26 · 2021: 31 · 2020: 29 · 2019: 28 · 2018: 3
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Genetics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by)
- Istituto Nazionale di Fisica Nucleare. Centro Nazionale Analisi Fotogrammi (cc-by)
- Funders
- Wellcome Trust (105281/Z/14/Z, 106130/Z/14/Z)
- University of Oxford
- Medical Research Council (MC_UU_00016/4, MR/R008108/1, MC_PC_15069, MC_UU_00016/1, MR/N00969X/1)
- National Human Genome Research Institute (R01HG003143)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- chromosome conformation capture, chromatin domains, regulatory hubs, enhancer-promoter interactions, distal enhancers, cis-regulatory elements, gene expression regulation, higher-order chromatin structure
- MeSH terms
- Alleles, Animals, Base Sequence, Binding Sites, Cells, Cultured, Chromatin, Enhancer Elements, Genetic, Female, Globins, Mice, Inbred C57BL, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors, Linkage Disequilibrium, Gene Expression Regulation, Developmental, Mice, Genetic Loci
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