Cited by 898Genomics and Chromatin DynamicsNuclear Structure and FunctionChromosomal and Genetic Variations

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

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Quinodoz, Sofia A., Ollikainen, Noah, Tabak, Barbara, Palla, Ali, Schmidt, Jan Marten, Detmar, Elizabeth, Lai, Mason M., Shishkin, Alexander A. +12 more·2018·Cell

Published version of a preprint

Abstract

Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.

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Crossref · 10.1016/j.cell.2018.05.024

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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 [403]

    The Results section reports that SPRITE measures simultaneous contacts among multiple DNA molecules and that larger clusters show interactions between distinct TADs; the Key Resources Table also identifies TAD triplets detected by GAM. But our copy does not say that the resolution of either method limits robust detection of individual CRUs. No page numbers are available in the indexed passages. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • Proximity ligation methods have played an important role in identifying key interactions, such as promoter and enhancer associations.

    “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 Quinodoz et al., 2018

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Authors
Quinodoz, S. A., Ollikainen, N., Tabak, B., Palla, A., Schmidt, J. M., Detmar, E., Lai, M. M., Shishkin, A. A., Bhat, P., Takei, Y., Trinh, V., Aznauryan, E., Russell, P., Cheng, C., Jovanovic, M., Chow, A., Cai, L., McDonel, P., Garber, M., & Guttman, M.
Affiliations
  • California Institute of Technology (US)
  • University of Massachusetts Chan Medical School (US)
  • Colorado School of Public Health (US)
  • Boston University (US)
Corresponding author
Guttman, Mitchell
Venue
Cell
Publisher
Elsevier BV
Published
2018-07
Volume
174
Issue
3
Pages
744-757.e24
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2806123558
Cited by
892
References
108
Citations by year
2026: 78 · 2025: 101 · 2024: 107 · 2023: 115 · 2022: 118 · 2021: 131 · 2020: 112 · 2019: 100 · 2018: 28
FWCI
33.35
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • HHMI Gilliam Fellowship
  • NSF GRFP Fellowship
  • NIGMS (T32 GM008042)
  • UCLA-Caltech MSTP (NIGMS T32 GM008042)
  • NIH 4DN Program (U01 DA040612, U01 HL130007)
  • NHGRI GGR Program (U01 HG007910)
  • New York Stem Cell Foundation (NYSCF-R-I13)
  • Sontag Foundation
  • Caltech
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
3D genome organization, interchromosomal interactions, nuclear bodies, nucleolus, nuclear speckles, sprites, long-range chromatin interactions, DNA packaging
MeSH terms
Cell Nucleolus, Cell Nucleus, Chromosome Mapping, Chromosomes, DNA, Humans, Structure-Activity Relationship, Genome, Eukaryota

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