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

Edward J. Banigan, Aafke A. van den Berg, Hugo B. Brandão, John F. Marko, Leonid A. Mirny*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Article numbere53558
JournaleLife
Volume9
DOIs
StatePublished - Apr 2020

Keywords

  • Chromosome organization
  • Cohesin
  • Condensin
  • Loop extrusion
  • Mitosis
  • TADs

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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