Fig. 5.

Model based on loop extrusion makes it possible to recapitulate Hi-C maps accurately using only CTCF ChIP-Seq results. (A, i and ii) Extrusion complex loads onto the fiber at a random locus, forming an extremely short-range loop. (A, iii) As the two subunits move in opposite directions along the fiber, the loop grows and the extruded fiber forms a domain. (A, iv) When a subunit detects a motif on the appropriate strand, it can stop sliding. Unlike diffusion, extrusion cannot mediate co-location of motifs on different chromosomes. (B) Three-dimensional rendering of a 3-Mb extrusion globule from the ensemble described below. Convergent CTCF anchors (orange spheres) lead to an unknotted loop spanning a compact, spatially segregated contact domain (highlighted in blue). (C) Contact probability vs. distance for 12 domains with a length of 1 Mb, created in silico using loop extrusion, measured from a 100-kb locus at the center of the domain. In each case, a power law is seen for distances between 5 kb and 400 kb. Mean ɣ = 0.72, SD = 0.06. (D) We use loop extrusion to model a 2.3-Mb region on chromosome 4 of GM12878. CTCF ChIP-Seq signals are normalized and converted into binding probabilities for the simulated extrusion complex. Each peak is assigned a forward (green) or reverse (red) orientation based on the strand of the underlying CTCF motif. Extrusion simulations yield an ensemble of 3D polymer configurations; contact maps for the simulated ensemble (Top) recapitulate the features observed in our kilobase-resolution Hi-C experiments (Bottom), including the position of domains and loops.