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. Author manuscript; available in PMC: 2021 Dec 10.
Published in final edited form as: Annu Rev Cell Dev Biol. 2021 Jul 6;37:199–232. doi: 10.1146/annurev-cellbio-032321-035734

Figure 1.

Figure 1

Formation of topologically associated domains (TADs). (a, right) Shown is a TAD that includes both active (blue) and inactive (red) chromatin. TADs are flanked by forward- and reverse-oriented boundary elements facing each other in a convergent orientation. CCCTC-binding factor (CTCF) binds to the flanking boundaries. (Top left) This inset shows an enlargement of the dark gray boxed region that highlights a chromatin loop extruded by cohesin. The loop contains stretches of active and inactive chromatin. (Bottom left) This inset shows an enlargement of the light gray boxed region that highlights a chromatin loop extruded by cohesin. The loop joins an enhancer and a promoter to initiate transcription by RNA polymerase II (Pol II). (b) Loop extrusion of chromatin by cohesin occurs in a stepwise fashion. ❶ Cohesin is loaded onto chromatin by the nipped B-like protein (NIPBL)-MAU2 complex. The cohesin loader remains engaged with cohesin throughout the loop-extrusion process and plays a role in loop stability. ❷ After loading, cohesin extrudes chromatin loops in a two-sided manner until ❸ it is blocked by CTCF or any other barrier protein. Cohesin is then released with the aid of the cohesin-release factor WAPL (not shown). (c–e) Condensin-mediated loop extrusion is predominantly one sided. As shown in panel c, purely one-sided loop extrusion by condensin generates much smaller loops than purely two-sided loop extrusion (see panel e) and is unable to achieve the levels of compaction required for mitotic condensation. As shown in panel d, effectively two-sided loop extrusion is proposed as an alternate model for efficient loop extrusion. The effectively two-sided model matches the values of the extrusion parameters. In this model, condensin subunits stochastically switch between extruding from one side and then extruding from the other. In any one instant, condensin extrudes in a one-sided manner, but on average the switching causes the asymmetric one-sided extrusion to be effectively two sided. Panel d shows three different levels of loop extrusion, in which the size of the extruded loop scales with the switching frequency. (f) A detailed schematic representation of stepwise asymmetric strand extrusion by condensin. The chromatin is color coded (green and purple) to help visualize the chromatin segments that are being alternately extruded.