Single-cell absolute contact probability detection reveals that chromosomes are organized by modulated stochasticity

Cattoni, D. I.; Cardozo Gizzi, A. M.; Georgieva, M.; Di Stefano, M.; Valeri, A.; Chamousset, D.; Houbron, C.; Dejardin, S.; Fiche, J.-B.; Marti-Renom, M. A.; Bantignies, F.; Cavalli, G.; Nollmann, M.

doi:10.1101/159814

bioRxiv · 10.1101/159814

Single-cell absolute contact probability detection reveals that chromosomes are organized by modulated stochasticity

Cattoni, D. I.·Cardozo Gizzi, A. M.·Georgieva, M.·Di Stefano, M.·Valeri, A.·Chamousset, D.·Houbron, C.·Dejardin, S.·Fiche, J.-B.·Marti-Renom, M. A.·Bantignies, F.·Cavalli, G.·Nollmann, M.

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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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Cattoni, D. I., Cardozo Gizzi, A. M., Georgieva, M., Di Stefano, M., Valeri, A., Chamousset, D., Houbron, C., Dejardin, S., Fiche, J.-B., Marti-Renom, M. A., Bantignies, F., Cavalli, G., Nollmann, M.. 2017-07-05. Single-cell absolute contact probability detection reveals that chromosomes are organized by modulated stochasticity. https://doi.org/10.1101/159814

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