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

Cattoni, Diego Ignacio; Cardozo Gizzi, Andrés M.; Georgieva, Mariya; Di Stefano, Marco; Valeri, Alessandro; Chamousset, Delphine; Houbron, Christophe; Déjardin, Stéphanie; Fiche, Jean Bernard; González, Inma Royo; Chang, Jia-Ming, 1978-; Sexton, Tom; Martí Renom, Marc A.; Bantignies, Frédéric; Cavalli, Giacomo; Nollmann, Marcelo

doi:http://dx.doi.org/10.1038/s41467-017-01962-x

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

Citation

Cattoni DI, Cardozo Gizzi AM, Georgieva M, Di Stefano M, Valeri A, Chamousset D et al. Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions. Nat Commun. 2017 Nov 24;8(1):1753. DOI: 10.1038/s41467-017-01962-x

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.