Fig. 4
Multi-scale whole nucleus simulations of chromosomes with compartments and loops. a Multi-scale whole nucleus simulation approach. Shown are simulation snapshots, where each of the 46 chromosomes is modeled as a polymer chain with a distinct color. Chromosome 1 is highlighted in blue, chromosome 2 in red. Simulations proceed in three consecutive phases. In phase 1, all chromosome chains are coarse grained, with 1 bead for every megabase of DNA, and t = 3 × 106 iterations of Langevin dynamics are computed. In phase 2, chromosome 1 is fine-grained progressively in five successive stages. At each stage, beads of chromosome 1 are replaced by 2 or 5 smaller beads, each representing 2 or 5 times smaller DNA segments, until each bead corresponds to 5 kb of DNA. All other 45 chromosomes are kept coarse-grained (1 Mb beads), and t = 105 iterations are computed at each stage. In phase 3, a specified number of loops can be formed by creating bonds between non-consecutive bead pairs, and t = 105 iterations are computed. Insets to either side of the green rectangle show a polymer segment featuring 3 loops in different colors (right) or no loops (left). The simulations in all three phases also include energy potentials to model the formation of A/B compartments. See “Methods” for details. b Contact frequency matrices for chromosome 1 as predicted by a simulation with compartments and 15 loops/Mb (logarithmic scale). Left: entire chromosome 1 with bins of 1 Mb. Alternating A/B compartments are clearly visible. Right: a 2.5-Mb region on chromosome 1 with bins of 25 kb. Blocks of enriched contact frequencies consistent with TADs are clearly seen along the diagonal. Color bar indicates the natural logarithm of counts per bin