RT Journal Article
SR Electronic
T1 Cell cycle dynamics of chromosomal organisation at single-cell resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 094466
DO 10.1101/094466
A1 Nagano, Takashi
A1 Lubling, Yaniv
A1 Varnai, Csilla
A1 Dudley, Carmel
A1 Leung, Wing
A1 Baran, Yael
A1 Mandelson-Cohen, Netta
A1 Wingett, Steven
A1 Fraser, Peter
A1 Tanay, Amos
YR 2016
UL http://biorxiv.org/content/early/2016/12/15/094466.abstract
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.