Cattoni, Diego IgnacioCardozo Gizzi, Andrés M.Georgieva, MariyaDi Stefano, MarcoValeri, AlessandroChamousset, DelphineHoubron, ChristopheDéjardin, StéphanieFiche, Jean BernardGonzález, Inma RoyoChang, Jia-Ming, 1978-Sexton, TomMartí Renom, Marc A.Bantignies, FrédéricCavalli, GiacomoNollmann, Marcelo2018-06-252018-06-252017Cattoni 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-x2041-1723http://hdl.handle.net/10230/34963At 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.application/pdfeng© The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-017-01962-xComputational biology and bioinformaticsEpigenomicsNanoscale biophysicsSuper-resolution microscopyinfo:eu-repo/semantics/openAccess