3D structures of individual mammalian genomes reveal principles of nuclear organization

The folding of genomic DNA from the beads-on-a-string like structure of nucleosomes into higher order assemblies is thought to be critically linked to nuclear processes, but it is unclear to what degree it is a cause or consequence of function. We have calculated the first 3D structural models of entire mammalian genomes using data from a new chromosome conformation capture protocol that allows us to first image and then process single cells. This has allowed us to study the folding of chromosomes down to a sub-100 kb scale. We show that the structures of individual topological-associated domains, chromosomes, and the way they pack together, varies very substantially from cell-to-cell. However, in all cells we find a consistent large-scale organization of compartments, with active enhancers and promoters clustering near inter-chromosomal interfaces, suggesting that nuclear processes such as transcription may drive chromosome and genome folding. ChIP-seq, RNA-seq and nuclear RNA-seq in haploid and diploid mouse embryonic stem cells