Abstract
SMC complexes, such as condensin or cohesin, organize chromatin throughout the cell cycle by a process known as loop extrusion. SMC complexes reel in DNA, extruding and progressively growing DNA loops. Modeling assuming two-sided loop extrusion reproduces key features of chromatin organization across different organisms. In vitro single-molecule experiments confirmed that yeast condensins extrude loops, however, they remain anchored to their loading sites and extrude loops in a “one-sided” manner. We therefore simulate one-sided loop extrusion to investigate whether “one-sided” complexes can compact mitotic chromosomes, organize interphase domains, and juxtapose bacterial chromosomal arms, as can be done by “two-sided” loop extruders. While one-sided loop extrusion cannot reproduce these phenomena, variants can recapitulate in vivo observations. We predict that SMC complexes in vivo constitute effectively two-sided motors or exhibit biased loading and propose relevant experiments. Our work suggests that loop extrusion is a viable general mechanism of chromatin organization.
Impact statement We reconcile seemingly contradictory findings of single-molecule and in vivo experiments on a major mechanism of chromosome organization by computationally investigating mechanisms of loop extrusion that are consistent with both.
Footnotes
We have added a section to discuss the organization of the yeast chromosome, as well as a more thorough discussion of the effects of transcription and SMC diffusion on the chromosome organization. Furthermore, new figures were added or updated: Figure 2 supplements 6 and 7 and Figure supplement 8.
