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

Diego I. Cattoni, Andrés M. Cardozo Gizzi, Mariya Georgieva, Marco 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 and Marcelo Nollmann ()
Additional contact information
Diego I. Cattoni: CNRS UMR5048, INSERM U1054, Université de Montpellier
Andrés M. Cardozo Gizzi: CNRS UMR5048, INSERM U1054, Université de Montpellier
Mariya Georgieva: CNRS UMR5048, INSERM U1054, Université de Montpellier
Marco Stefano: Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Alessandro Valeri: CNRS UMR5048, INSERM U1054, Université de Montpellier
Delphine Chamousset: CNRS UMR5048, INSERM U1054, Université de Montpellier
Christophe Houbron: CNRS UMR5048, INSERM U1054, Université de Montpellier
Stephanie Déjardin: CNRS UMR5048, INSERM U1054, Université de Montpellier
Jean-Bernard Fiche: CNRS UMR5048, INSERM U1054, Université de Montpellier
Inma González: CNRS UMR 9002, Université de Montpellier
Jia-Ming Chang: CNRS UMR 9002, Université de Montpellier
Thomas Sexton: CNRS UMR 9002, Université de Montpellier
Marc A. Marti-Renom: Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Frédéric Bantignies: CNRS UMR 9002, Université de Montpellier
Giacomo Cavalli: CNRS UMR 9002, Université de Montpellier
Marcelo Nollmann: CNRS UMR5048, INSERM U1054, Université de Montpellier

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract At the kilo- to megabase pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combine 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 find 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 are able to visualize nanometer-sized epigenetic domains at the single-cell level. In addition, absolute contact frequencies within and between TADs are 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.

Date: 2017
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DOI: 10.1038/s41467-017-01962-x

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