PT  - JOURNAL ARTICLE
AU  - Nagano, Takashi
AU  - Lubling, Yaniv
AU  - Varnai, Csilla
AU  - Dudley, Carmel
AU  - Leung, Wing
AU  - Baran, Yael
AU  - Mandelson-Cohen, Netta
AU  - Wingett, Steven
AU  - Fraser, Peter
AU  - Tanay, Amos
TI  - Cell cycle dynamics of chromosomal organisation at single-cell resolution
AID  - 10.1101/094466
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 094466
4099  - http://biorxiv.org/content/early/2016/12/15/094466.short
4100  - http://biorxiv.org/content/early/2016/12/15/094466.full
AB  - Chromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between a highly condensed mitotic structure facilitating chromosome segregation, and a decondensed interphase structure accommodating transcription, gene silencing and DNA replication. These cyclical structural transformations have been evident under the microscope for over a century, but their molecular-level analysis is still lacking. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological domains (TADs), contact insulation and long-range loops, all defined by ensemble Hi-C maps, are governed by distinct cell cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Analysing whole genome 3D structural models using haploid cell data, we discover a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data creates an essential new paradigm for the re-interpretation of chromosome conformation maps through the prism of the cell cycle.