1. Chromosomes and Gene Expression
  2. Physics of Living Systems

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

  1. Edward J Banigan
  2. Aafke A van den Berg
  3. Hugo B Brandão
  4. John F Marko
  5. Leonid A Mirny  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. Harvard University, United States
  3. Northwestern University, United States
https://doi.org/10.7554/eLife.53558
Share this article
Cite this article
  1. Edward J Banigan
  2. Aafke A van den Berg
  3. Hugo B Brandão
  4. John F Marko
  5. Leonid A Mirny
(2020)
Chromosome organization by one-sided and two-sided loop extrusion
eLife 9:e53558.
https://doi.org/10.7554/eLife.53558
  2. Download BibTeX
  3. Download .RIS

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

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5478-7425

  2. 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.

  3. Hugo B Brandão

    Graduate Program in Biophysics, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5496-0638

  4. 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.

  5. 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.
    ORCID icon "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

  1. Kevin Struhl, Harvard Medical School, United States

Publication history

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

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.

Metrics

  • 4,781
    Page views
  • 787
    Downloads
  • 51
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Edward J Banigan
  2. Aafke A van den Berg
  3. Hugo B Brandão
  4. John F Marko
  5. Leonid A Mirny
(2020)
Chromosome organization by one-sided and two-sided loop extrusion
eLife 9:e53558.
https://doi.org/10.7554/eLife.53558

Categories and tags

Research organisms

Further reading

    1. Chromosomes and Gene Expression
    2. Plant Biology

    Vernalization-triggered expression of the antisense transcript COOLAIR is mediated by CBF genes

    Myeongjune Jeon, Goowon Jeong ... Ilha Lee
    Research Article Updated

    To synchronize flowering time with spring, many plants undergo vernalization, a floral-promotion process triggered by exposure to long-term winter cold. In Arabidopsis thaliana, this is achieved through cold-mediated epigenetic silencing of the floral repressor, FLOWERING LOCUS C (FLC). COOLAIR, a cold-induced antisense RNA transcribed from the FLC locus, has been proposed to facilitate FLC silencing. Here, we show that C-repeat (CRT)/dehydration-responsive elements (DREs) at the 3′-end of FLC and CRT/DRE-binding factors (CBFs) are required for cold-mediated expression of COOLAIR. CBFs bind to CRT/DREs at the 3′-end of FLC, both in vitro and in vivo, and CBF levels increase gradually during vernalization. Cold-induced COOLAIR expression is severely impaired in cbfs mutants in which all CBF genes are knocked-out. Conversely, CBF-overexpressing plants show increased COOLAIR levels even at warm temperatures. We show that COOLAIR is induced by CBFs during early stages of vernalization but COOLAIR levels decrease in later phases as FLC chromatin transitions to an inactive state to which CBFs can no longer bind. We also demonstrate that cbfs and FLCΔCOOLAIR mutants exhibit a normal vernalization response despite their inability to activate COOLAIR expression during cold, revealing that COOLAIR is not required for the vernalization process.

    1. Chromosomes and Gene Expression

    X-chromosome target specificity diverged between dosage compensation mechanisms of two closely related Caenorhabditis species

    Qiming Yang, Te-Wen Lo ... Barbara J Meyer
    Research Article

    An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species C. briggsae (Cbr) and C. elegans (Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs within Cbr DCC recruitment sites that are highly enriched on X: 13-bp MEX and 30-bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can determine whether Cel DCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with conservation of target specificity for X-chromosome dosage compensation across Drosophila species and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.

    1. Chromosomes and Gene Expression
    2. Plant Biology

    Flowering: Keeping it cool

    Vy Nguyen, Iain Searle
    Insight

    A well-established model for how plants start the process of flowering in periods of cold weather may need revisiting.