Mechanisms of insulation and facilitation.

(A) (top) Illustration of the insulation mechanism: strong dynamic steric exclusion by a chromatin loop is shown by a superposition of loops in multiple conformations (grey, with enhancer and promoter) and their sterically excluded region (dashed lines), surrounded by other distal regions of chromatin (grey). (bottom) Density of distal monomers (i.e. outside the loop and>10 kb from the loop base) as a function of radial distance from the center of mass of the loop. The loop-free control exactly repeats this procedure for an equivalent region without a loop. Both are normalized using respective radial-position dependent spatial density (Methods). (B) (top) Illustration of facilitation mechanism: an E-P pair flanking a loop has an effectively shorter genomic distance; here an E-P pair with 50 kb separation and a 30 kb loop behaves similarly to an E-P pair separated by 20 kb in a region without a loop. (bottom) Comparison of contact frequency ratios for the above situations, as a function of E-P distance. (C) Simulated cumulative distribution of spatial distances (in silico FISH) for an E-P pair with a genomic distance of 90 kb.