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Single-cell absolute contact probability detection reveals that chromosomes are organized by multiple, low-frequency yet specific interactions

View ORCID ProfileDiego I. Cattoni, Andrés M. Cardozo Gizzi, Mariya Georgieva, Marco Di Stefano, Alessandro Valeri, Delphine Chamousset, Christophe Houbron, Stephanie Déjardin, Jean-Bernard Fiche, Inma González, Jia-Ming Chang, Thomas Sexton, Marc A. Marti-Renom, Frédéric Bantignies, Giacomo Cavalli, Marcelo Nollmann
doi: https://doi.org/10.1101/159814
Diego I. Cattoni
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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  • ORCID record for Diego I. Cattoni
Andrés M. Cardozo Gizzi
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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Mariya Georgieva
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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Marco Di Stefano
2CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain; Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain
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Alessandro Valeri
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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Delphine Chamousset
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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Christophe Houbron
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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Stephanie Déjardin
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
3Institut de Génétique Humaine, CNRS UMR 9002, Université de Montpellier, 141 rue de la Cardonille, 34396 Montpellier, France
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Jean-Bernard Fiche
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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Inma González
3Institut de Génétique Humaine, CNRS UMR 9002, Université de Montpellier, 141 rue de la Cardonille, 34396 Montpellier, France
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Jia-Ming Chang
3Institut de Génétique Humaine, CNRS UMR 9002, Université de Montpellier, 141 rue de la Cardonille, 34396 Montpellier, France
4Department of Computer Science, National Chengchi University, 11605 Taipei City, Taiwan
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Thomas Sexton
3Institut de Génétique Humaine, CNRS UMR 9002, Université de Montpellier, 141 rue de la Cardonille, 34396 Montpellier, France
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Marc A. Marti-Renom
2CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain; Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain
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Frédéric Bantignies
3Institut de Génétique Humaine, CNRS UMR 9002, Université de Montpellier, 141 rue de la Cardonille, 34396 Montpellier, France
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Giacomo Cavalli
3Institut de Génétique Humaine, CNRS UMR 9002, Université de Montpellier, 141 rue de la Cardonille, 34396 Montpellier, France
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Marcelo Nollmann
1Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
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  • For correspondence: marcelo.nollmann@cbs.cnrs.fr
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Abstract

At the kilo- to mega-base pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combined high-content super-resolution microscopies with state-of-the-art DNA labeling methods to reveal the variability in the multiscale organization of the Drosophila genome. We found that association frequencies within TADs and between TAD borders are below ~10%, independently of TAD size, epigenetic state, or cell type. Critically, despite this large heterogeneity, we were able to visualize nanometer-sized epigenetic domains at the single-cell level. In addition, absolute contact frequencies within and between TADs were to a large extent defined by genomic distance, higher-order chromosome architecture, and epigenetic identity. We propose that TADs and compartments are organized by multiple, small frequency, yet specific interactions that are regulated by epigenetics and transcriptional state.

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Posted October 24, 2017.
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Single-cell absolute contact probability detection reveals that chromosomes are organized by multiple, low-frequency yet specific interactions
Diego I. Cattoni, Andrés M. Cardozo Gizzi, Mariya Georgieva, Marco Di Stefano, Alessandro Valeri, Delphine Chamousset, Christophe Houbron, Stephanie Déjardin, Jean-Bernard Fiche, Inma González, Jia-Ming Chang, Thomas Sexton, Marc A. Marti-Renom, Frédéric Bantignies, Giacomo Cavalli, Marcelo Nollmann
bioRxiv 159814; doi: https://doi.org/10.1101/159814
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Single-cell absolute contact probability detection reveals that chromosomes are organized by multiple, low-frequency yet specific interactions
Diego I. Cattoni, Andrés M. Cardozo Gizzi, Mariya Georgieva, Marco Di Stefano, Alessandro Valeri, Delphine Chamousset, Christophe Houbron, Stephanie Déjardin, Jean-Bernard Fiche, Inma González, Jia-Ming Chang, Thomas Sexton, Marc A. Marti-Renom, Frédéric Bantignies, Giacomo Cavalli, Marcelo Nollmann
bioRxiv 159814; doi: https://doi.org/10.1101/159814

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