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Cited by 715Genomics and Chromatin DynamicsChromatin Remodeling and CancerChromosomal and Genetic Variations

Complex multi-enhancer contacts captured by genome architecture mapping

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Beagrie, Robert A., Scialdone, Antonio, Schueler, Markus, Kraemer, Dorothee C. A., Chotalia, Mita, Xie, Sheila Q., Barbieri, Mariano, de Santiago, Inês +9 more·2017·Nature
DOI 10.1038/nature21411PMC PMC5366070
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Abstract

The organization of the genome in the nucleus and the interactions of genes with their regulatory elements are key features of transcriptional control and their disruption can cause disease. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We apply GAM to mouse embryonic stem cells and identify enrichment for specific interactions between active genes and enhancers across very large genomic distances using a mathematical model termed SLICE (statistical inference of co-segregation). GAM also reveals an abundance of three-way contacts across the genome, especially between regions that are highly transcribed or contain super-enhancers, providing a level of insight into genome architecture that, owing to the technical limitations of current technologies, has previously remained unattainable. Furthermore, GAM highlights a role for gene-expression-specific contacts in organizing the genome in mammalian nuclei.

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  • Both GAM and SPRITE could successfully reveal multi-way contacts across TADs and chromosomes, but their resolution currently limits robust detection of individual CRUs.

    “While both methods could successfully reveal multi-way contacts across TADs and chromosomes, their resolution currently limits robust detection of individual CRUs.”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [497]

    In ‘Detecting interacting triplets’ (page unavailable), the paper reports that GAM detects simultaneous multi-way contacts between TADs, but that the current dataset resolves triplets only at hundreds-of-kilobases scale; the Discussion says larger datasets could enable higher resolution. The paper does not assess SPRITE or detection of individual CRUs, and its TAD-triplet analysis is restricted to TADs on the same chromosome, so it does not establish the full claim about both methods and contacts across chromosomes. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Genome Architecture Mapping (GAM) enables probing multi-way chromosomal contacts.

    “Genome Architecture Mapping (GAM) is one technique that enables probing multi-way chromosomal contacts [497].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [497]

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Authors
Beagrie, R. A., Scialdone, A., Schueler, M., Kraemer, D. C. A., Chotalia, M., Xie, S. Q., Barbieri, M., de Santiago, I., Lavitas, L.-M., Branco, M. R., Fraser, J., Dostie, J., Game, L., Dillon, N., Edwards, P. A. W., Nicodemi, M., & Pombo, A.
Affiliations
  • Max Delbrück Center (DE)
  • Istituto Nazionale di Fisica Nucleare, Sezione di Napoli (IT)
  • Hammersmith Hospital (GB)
  • McGill University (CA)
  • University of Cambridge (GB)
Corresponding author
  • Nicodemi, Mario
  • Pombo, Ana
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-03
Volume
543
Issue
7646
Pages
519-524
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature21411
PMC
PMC5366070
OpenAlex
W2594764564
Cited by
715
References
7
Citations by year
2026: 53 · 2025: 59 · 2024: 54 · 2023: 76 · 2022: 99 · 2021: 108 · 2020: 80 · 2019: 83 · 2018: 70 · 2017: 31
FWCI
29.50
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
Breast Cancer Campaign (2006MAYSP10)
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
3D genome organization, chromatin interactions, enhancer-gene interactions, super-enhancers, mouse embryonic stem cells
MeSH terms
Mouse Embryonic Stem Cells, Animals, Chromatin, Chromosome Mapping, Enhancer Elements, Genetic, Male, Models, Genetic, Transcription, Genetic, Genome, Sequence Analysis, DNA, Epigenesis, Genetic, Mice

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