The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Visualizing DNA folding and RNA in embryos at single-cell resolution
Open accessAbstract
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.
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“It also follows from these models that the frequency of enhancer–promoter contacts may have non-linear effects on transcriptional output, consistent with experimental observations [405, 503].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [503]
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“advances in super-resolution imaging (reviewed in [500]) now enable the visualisation of multiple interacting loci to the resolution of a few kilobases in single cells [448, 501–503].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [503]
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Cites
(2008) · Journal of Machine Learning Research · Cited by 33,051
(1996) · Cited by 20,179
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
A gene complex controlling segmentation in Drosophila
Lewis, E. B. (1978) · Nature · doi:10.1038/276565a0 · Cited by 3,813
Spatially resolved, highly multiplexed RNA profiling in single cells
Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S., & Zhuang, X. (2015) · Science · doi:10.1126/science.aaa6090 · Cited by 2,969
Self-citationSpatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895
Three-dimensional folding and functional organization principles of the Drosophila genome
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012) · Cell · doi:10.1016/j.cell.2012.01.010 · Cited by 1,983
Multiscale 3D Genome Rewiring during Mouse Neural Development
Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G. L., Lubling, Y., Xu, X., Lv, X., Hugnot, J.-P., Tanay, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.043 · Cited by 1,338
Highly inclined thin illumination enables clear single-molecule imaging in cells
Tokunaga, M., Imamoto, N., & Sakata-Sogawa, K. (2008) · Nature Methods · doi:10.1038/nmeth1171 · Cited by 1,331
Research works printed but not linked: 2
- Beliveau, B. J. et al. in Super-Resolution Microscopy: Methods and Protocols (ed. Erfle, H.) 231–252 (Springer, New York, 2017).
- Ester, M., Kriegel, H.-P., Sander, J. & Xu, X. A density-based algorithm for discovering clusters. KDD-96 Proc. 226–231 (1996).
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Metadata
- Authors
- Mateo, L. J., Murphy, S. E., Hafner, A., Cinquini, I. S., Walker, C. A., & Boettiger, A. N.
- Affiliations
- Stanford University (US)
- Corresponding author
- Boettiger, Alistair N.
- Venue
- Nature
- Published
- 2019-03-18
- Volume
- 568
- Issue
- 7750
- Pages
- 49-54
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6556380
- OpenAlex
- W2921773684
- Cited by
- 446
- References
- 62
- Citations by year
- 2026: 43 · 2025: 53 · 2024: 57 · 2023: 61 · 2022: 59 · 2021: 71 · 2020: 68 · 2019: 31
- FWCI
- 19.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (1dp2gm132935-01)
- National Institute of General Medical Sciences (DP2 GM132935)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- DNA folding, chromatin structure, polycomb repressive complex, Hox gene clusters, Drosophila embryo, enhancer-promoter interactions, RNA localization, developmental gene regulation, transcriptional repression
- MeSH terms
- Animals, Chromatin, DNA, Drosophila melanogaster, Enhancer Elements, Genetic, Female, Genes, Homeobox, Multigene Family, Male, Nucleic Acid Conformation, Organ Specificity, Promoter Regions, Genetic, RNA, Transcription, Genetic, Gene Expression Regulation, Developmental, Genome, Insect, Single-Cell Analysis, Polycomb-Group Proteins
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