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Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus
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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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“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]
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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 Quinodoz et al., 2018
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p53 mediates target gene association with nuclear speckles for amplified RNA expression
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HiChIRP reveals RNA-associated chromosome conformation
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Metadata
- 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
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 174
- Issue
- 3
- Pages
- 744-757.e24
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6548320
- 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
- bronze
- doi.org
- Licence
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › 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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