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

eLife

John F Marko¹  Aafke A van den Berg¹  Leonid A Mirny²  Hugo B Brandão³  Edward J Banigan³ 

[1] Department of Physics, Massachusetts Institute of Technology, Cambridge, United States;Harvard Graduate Program in Biophysics, Harvard University, Cambridge, United States;Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, United States;

关键词: loop extrusion;    cohesin;    condensin;    chromosome organization;    mitosis;    TADs;   

DOI  :  10.7554/eLife.53558

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown