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

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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.

The following previously published data sets were used

1. Bonev B et al
(2017) Multi-scale 3D genome rewiring during mouse neural development
NCBI Gene Expression Omnibus, GSE96107.

https://www.ncbi.nlm.nih.gov/geo/
1. Wang X
2. Rudner DZ
(2015) Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilis
NCBI Gene Expression Omnibus, GSE68418.

https://www.ncbi.nlm.nih.gov/geo/
1. M Ohno et al
(2019) Studies on chromosome structure at sub-nucleosome level
NCBI Bioproject, PRJNA427106.

https://www.ncbi.nlm.nih.gov/bioproject

Article and author information

Author details

Edward J Banigan

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5478-7425
Aafke A van den Berg

Department of Physics and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Hugo B Brandão

Graduate Program in Biophysics, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5496-0638
John F Marko

Department of Molecular Biosciences, Department of Physics and Astronomy, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.
Leonid A Mirny

Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, Cambridge, United States

For correspondence
lmirny@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0785-5410

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.

Reviewing Editor

Kevin Struhl, Harvard Medical School, United States

Version history

Received: November 13, 2019
Accepted: April 3, 2020
Accepted Manuscript published: April 6, 2020 (version 1)
Version of Record published: June 15, 2020 (version 2)

Copyright

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.