Figure 1. CTCF and cohesins build chromatin architecture.

(A) Model of Topologically Associating Domains (TAD). TADs are regions of strong self‐contact. Promoter–enhancer interactions inside the domains are favoured while contacts with promoters and enhancers in adjacent domains are restrained. This is believed to help establish a functional organization of the genome. (B) Hi‐C profile illustrating TAD organization at an example locus in Neural Progenitor cells (data from Bonev et al, ²⁰¹⁷). Increasing colour strength denotes enhanced interaction frequency. This in turn, can be interpreted as increased physical proximity in the three‐dimensional space of the cell nucleus. Triangles of Hi‐C signal reveal domains of enhanced interaction frequencies (TADs). Dots in the matrix (corner peaks) correspond to loops and reveal interactions between relatively short genomic intervals (here sub‐TAD boundaries). At some loci, TAD boundaries interact heavily with the entire TAD, which manifests itself as thin stripes of increased interaction frequency. (C) Loop extrusion model. Upon loading, cohesins (yellow ring) start translocating on chromatin (arrows) and their movement is accompanied by extrusion of an ever‐growing loop. Cohesins pass CTCF proteins bound to a motif which does not face them. Loop extrusion stops when cohesins encounter CTCF bound to a motif that is facing them (thick black arrow). (D) Model explaining the formation of architectural stripes. At genomic locations where cohesin loading occurs in the proximity of CTCF‐binding sites, including at active enhancers (green rectangle), CTCF bound to a motif oriented in a forward direction (en face) with respect to the loaded cohesin blocks loop extrusion immediately after loading. Loop extrusion proceeds fuelled by cohesin activity on the other side of the complex and allows the elements in the entire domain including promoters (red rectangle) to be “presented” to the fixed anchor overlapping the active enhancer (green rectangle). Depicted here is a single cohesin ring, it is unclear whether one or two cohesin rings extrude loops.