Figure 1

Proposed model for genome folding dynamics during the cell cycle. In interphase genome folding is defined by locus-specific compartments and chromatin loops. A/B-compartments and promoter-enhancer loops are cell type-specific, whereas topologically associating domains (TADs) are more tissue-invariant. In prophase many chromatin complexes dissociate from the chromosome, the interphase chromosome organization is lost and replaced by a locus-independent, universal, and cell type-invariant mitotic structure. Mitotic chromosomes form longitudinally compressed stochastically positioned loop arrays. Although mitotic chromosome folding is locus-independent and universal, specific loci, such as TAD boundaries, and cell type-specific elements, such as enhancers, remain marked. In early G1 the mitotic chromosome decondenses again. Next, TAD boundaries are re-activated and TADs are re-established. Subsequently, promoter and enhancer re-associate with transcription factors and other complexes and promoter-enhancer interactions are re-established. At the same time, groups of active and inactive TADs self-assemble into higher order structures corresponding to A- and B-compartments, respectively. This model of the order of events is currently hypothetical and based on theoretical considerations (see text). The figure of the mitotic chromosome was made by Maxim Imakaev, Geoff Fudenberg, Natalia Naumova, and Leonid Mirny.