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

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 acros...

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Autores principales: Banigan, Edward J, van den Berg, Aafke A, Brandão, Hugo B, Marko, John F, Mirny, Leonid A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295573/
https://www.ncbi.nlm.nih.gov/pubmed/32250245
http://dx.doi.org/10.7554/eLife.53558
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author Banigan, Edward J
van den Berg, Aafke A
Brandão, Hugo B
Marko, John F
Mirny, Leonid A
author_facet Banigan, Edward J
van den Berg, Aafke A
Brandão, Hugo B
Marko, John F
Mirny, Leonid A
author_sort Banigan, Edward J
collection PubMed
description 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.
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spelling pubmed-72955732020-06-17 Chromosome organization by one-sided and two-sided loop extrusion Banigan, Edward J van den Berg, Aafke A Brandão, Hugo B Marko, John F Mirny, Leonid A eLife Chromosomes and Gene Expression 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. eLife Sciences Publications, Ltd 2020-04-06 /pmc/articles/PMC7295573/ /pubmed/32250245 http://dx.doi.org/10.7554/eLife.53558 Text en © 2020, Banigan et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Banigan, Edward J
van den Berg, Aafke A
Brandão, Hugo B
Marko, John F
Mirny, Leonid A
Chromosome organization by one-sided and two-sided loop extrusion
title Chromosome organization by one-sided and two-sided loop extrusion
title_full Chromosome organization by one-sided and two-sided loop extrusion
title_fullStr Chromosome organization by one-sided and two-sided loop extrusion
title_full_unstemmed Chromosome organization by one-sided and two-sided loop extrusion
title_short Chromosome organization by one-sided and two-sided loop extrusion
title_sort chromosome organization by one-sided and two-sided loop extrusion
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295573/
https://www.ncbi.nlm.nih.gov/pubmed/32250245
http://dx.doi.org/10.7554/eLife.53558
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