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bioRxiv · 10.1101/094466

Cell cycle dynamics of chromosomal organisation at single-cell resolution

Nagano, T.·Lubling, Y.·Varnai, C.·Dudley, C.·Leung, W.·Baran, Y.·Mandelson Cohen, N.·Wingett, S.·Fraser, P.·Tanay, A.
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Abstract

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.

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Nagano, T., Lubling, Y., Varnai, C., Dudley, C., Leung, W., Baran, Y., Mandelson Cohen, N., Wingett, S., Fraser, P., Tanay, A.. 2016-12-15. Cell cycle dynamics of chromosomal organisation at single-cell resolution. https://doi.org/10.1101/094466

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