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Visualizing DNA folding and RNA in embryos at single-cell resolution

Author

Listed:
  • Leslie J. Mateo

    (Stanford University)

  • Sedona E. Murphy

    (Stanford University
    Stanford University)

  • Antonina Hafner

    (Stanford University)

  • Isaac S. Cinquini

    (Stanford University
    Stanford University)

  • Carly A. Walker

    (Stanford University)

  • Alistair N. Boettiger

    (Stanford University)

Abstract

The establishment of cell types during development requires precise interactions between genes and distal regulatory sequences. We have a limited understanding of how these interactions look in three dimensions, vary across cell types in complex tissue, and relate to transcription. Here we describe optical reconstruction of chromatin architecture (ORCA), a method that can trace the DNA path in single cells with nanoscale accuracy and genomic resolution reaching two kilobases. We used ORCA to study a Hox gene cluster in cryosectioned Drosophila embryos and labelled around 30 RNA species in parallel. We identified cell-type-specific physical borders between active and Polycomb-repressed DNA, and unexpected Polycomb-independent borders. Deletion of Polycomb-independent borders led to ectopic enhancer–promoter contacts, aberrant gene expression, and developmental defects. Together, these results illustrate an approach for high-resolution, single-cell DNA domain analysis in vivo, identify domain structures that change with cell identity, and show that border elements contribute to the formation of physical domains in Drosophila.

Suggested Citation

  • Leslie J. Mateo & Sedona E. Murphy & Antonina Hafner & Isaac S. Cinquini & Carly A. Walker & Alistair N. Boettiger, 2019. "Visualizing DNA folding and RNA in embryos at single-cell resolution," Nature, Nature, vol. 568(7750), pages 49-54, April.
  • Handle: RePEc:nat:nature:v:568:y:2019:i:7750:d:10.1038_s41586-019-1035-4
    DOI: 10.1038/s41586-019-1035-4
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    Cited by:

    1. Gerard Llimos & Vincent Gardeux & Ute Koch & Judith F. Kribelbauer & Antonina Hafner & Daniel Alpern & Joern Pezoldt & Maria Litovchenko & Julie Russeil & Riccardo Dainese & Riccardo Moia & Abdurraouf, 2022. "A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Guang Shi & D. Thirumalai, 2023. "A maximum-entropy model to predict 3D structural ensembles of chromatin from pairwise distances with applications to interphase chromosomes and structural variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Robin Aguilar & Conor K. Camplisson & Qiaoyi Lin & Karen H. Miga & William S. Noble & Brian J. Beliveau, 2024. "Tigerfish designs oligonucleotide-based in situ hybridization probes targeting intervals of highly repetitive DNA at the scale of genomes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Olivier Messina & Flavien Raynal & Julian Gurgo & Jean-Bernard Fiche & Vera Pancaldi & Marcelo Nollmann, 2023. "3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Lindsay Lee & Hongyu Yu & Bojing Blair Jia & Adam Jussila & Chenxu Zhu & Jiawen Chen & Liangqi Xie & Antonina Hafner & Shreya Mishra & Duan Dennis Wang & Caterina Strambio-De-Castillia & Alistair Boet, 2023. "SnapFISH: a computational pipeline to identify chromatin loops from multiplexed DNA FISH data," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    6. Li-Hsin Chang & Sourav Ghosh & Andrea Papale & Jennifer M. Luppino & Mélanie Miranda & Vincent Piras & Jéril Degrouard & Joanne Edouard & Mallory Poncelet & Nathan Lecouvreur & Sébastien Bloyer & Amél, 2023. "Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Matthew Antel & Romir Raj & Madona Y. G. Masoud & Ziwei Pan & Sheng Li & Barbara G. Mellone & Mayu Inaba, 2022. "Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Sora Yoon & Aditi Chandra & Golnaz Vahedi, 2022. "Stripenn detects architectural stripes from chromatin conformation data using computer vision," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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