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Cited by 562Genomics and Chromatin DynamicsAdvanced Fluorescence Microscopy TechniquesSingle-cell and spatial transcriptomics

Genome-Scale Imaging of the 3D Organization and Transcriptional Activity of Chromatin

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Su, Jun-Han, Zheng, Pu, Kinrot, Seon S., Bintu, Bogdan, Zhuang, Xiaowei·2020·Cell
DOI 10.1016/j.cell.2020.07.032PMC PMC7851072
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Abstract

The 3D organization of chromatin regulates many genome functions. Our understanding of 3D genome organization requires tools to directly visualize chromatin conformation in its native context. Here we report an imaging technology for visualizing chromatin organization across multiple scales in single cells with high genomic throughput. First we demonstrate multiplexed imaging of hundreds of genomic loci by sequential hybridization, which allows high-resolution conformation tracing of whole chromosomes. Next we report a multiplexed error-robust fluorescence in situ hybridization (MERFISH)-based method for genome-scale chromatin tracing and demonstrate simultaneous imaging of more than 1,000 genomic loci and nascent transcripts of more than 1,000 genes together with landmark nuclear structures. Using this technology, we characterize chromatin domains, compartments, and trans-chromosomal interactions and their relationship to transcription in single cells. We envision broad application of this high-throughput, multi-scale, and multi-modal imaging technology, which provides an integrated view of chromatin organization in its native structural and functional context.

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  • A recently developed oligopainting strategy combined with super-resolution microscopy allows the path of the chromatin fibril to be traced at relatively long genomic loci.

    “A recently developed oligopainting strategy [149] combined with super-resolution microscopy allows the path of the chromatin fibril to be traced at relatively long genomic loci [150,151].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [151]

    The Results section, “High-Resolution Chromatin Tracing of Whole Chromosomes” (page unavailable), reports tracing chromosome 21 across approximately 650 loci using oligonucleotide probes and sequential imaging, supporting the claim that long genomic regions can be traced. The paper describes a fluorescence microscope and sequential FISH, but our copy does not establish that this tracing used super-resolution microscopy. The separate oligopainting citation [149] is not assessed here. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Su, J.-H., Zheng, P., Kinrot, S. S., Bintu, B., & Zhuang, X.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
  • Bintu, Bogdan
  • Zhuang, Xiaowei
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2020-09
Volume
182
Issue
6
Pages
1641-1659.e26
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2020.07.032
PMC
PMC7851072
OpenAlex
W3050508217
Cited by
562
References
11
Citations by year
2026: 88 · 2025: 98 · 2024: 127 · 2023: 82 · 2022: 76 · 2021: 78 · 2020: 13
FWCI
20.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
3D genome organization, chromatin conformation, single-cell imaging, MERFISH, chromatin domains, chromatin compartments, nascent RNA, transcription, single-cell transcriptomics
MeSH terms
Algorithms, Cell Line, Cell Nucleus, Chromatin, Chromosomes, Human, DNA, Humans, Image Processing, Computer-Assisted, Molecular Conformation, Nucleolus Organizer Region, RNA, Software, In Situ Hybridization, Fluorescence, Genomics, High-Throughput Screening Assays, Single-Cell Analysis, Multimodal Imaging

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