Chromosome organization by one-sided and two-sided loop extrusion

SMC complexes organize chromatin throughout the cell cycle across many cell types. Experiments indicate that this is achieved by an energy-consuming process known as loop extrusion, in which SMC complexes, such as condensin or cohesin, reel in DNA/chromatin, extruding and progressively growing a DNA/chromatin loop. Theoretical modeling assuming two-sided loop extrusion has successfully reproduced key features of chromatin organization across different organisms. Recent in vitro single-molecule experiments confirmed that yeast condensins extrude loops. However, condensins remain anchored to their initial loading sites, so that they extrude loops in an asymmetric, “one-sided” manner. This raises the question of whether such “one-sided” complexes are able to perform the many functions that are commonly attributed to “two-sided” loop-extruding factors in vivo, such as mitotic chromosome compaction, interphase topologically associated domain formation, and bacterial chromosomal arm juxtaposition. We simulated one-sided loop extrusion and its variants in 3D models of chromosome organization in these scenarios. We found that while pure one-sided loop extrusion is unable to reproduce these phenomena, variants of one-sided extrusion that approximate two-sided extrusion can recover in vivo observations. We propose experiments that can test our quantitative predictions, and we predict that SMC complexes in vivo may constitute effectively two-sided motors and/or exhibit biased loading. Our work suggests that loop extrusion remains a viable general mechanism of chromatin organization.