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

CATTONI, DIEGO I.*; CARDOZO GIZZI, ANDRÉS M.*; GEORGIEVA, MARIYA*; DI STEFANO, MARCO; VALERI, ALESSANDRO; CHAMOUSSET, DELPHINE; HOUBRON, CHRISTOPHE; DÉJARDIN, STEPHANIE; FICHE, JEAN-BERNARD; GONZÁLEZ, INMA; CHANG, JIA-MING; SEXTON, THOMAS; MARTI-RENOM, MARC A.; BANTIGNIES, FRÉDÉRIC; CAVALLI, GIACOMO; NOLLMANN, MARCELO

NATURE COMMUNICATIONS

Nature Publishing Group

Año: 2017 vol. 8

2041-1723

t 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 st