Chromosome organization by one-sided and two-sided loop extrusion
- Massachusetts Institute of Technology, United States
- Harvard University, United States
- Northwestern University, United States
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.
Data availability
Simulation and analysis code used to produce and analyze data has been made publicly available on GitHub. Methods and code documentation explains usage. In Figure 3, we show Hi-C data from another publication with GEO accession number GSE96107. In Figure 3 - figure supplement 8, we show Hi-C data from another publication with Bioproject accession number PRJNA427106. In Figure 4, we show Hi-C data from another publication with GEO accession number GSE68418.
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Multi-scale 3D genome rewiring during mouse neural developmentNCBI Gene Expression Omnibus, GSE96107.
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Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilisNCBI Gene Expression Omnibus, GSE68418.
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Studies on chromosome structure at sub-nucleosome levelNCBI Bioproject, PRJNA427106.
Article and author information
Author details
Funding
National Institutes of Health (U54DK107980)
- Edward J Banigan
- Aafke A van den Berg
- Hugo B Brandão
- John F Marko
- Leonid A Mirny
National Institutes of Health (U54CA193419)
- Edward J Banigan
- Aafke A van den Berg
- Hugo B Brandão
- John F Marko
- Leonid A Mirny
National Institutes of Health (GM114190)
- Edward J Banigan
- Aafke A van den Berg
- Hugo B Brandão
- Leonid A Mirny
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Banigan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Chromosome organization by one-sided and two-sided loop extrusion
eLife 9:e53558.
https://doi.org/10.7554/eLife.53558
Further reading
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