Random sub-diffusion and capture of genes by the nuclear pore reduces dynamics and coordinates interchromosomal movement

  1. Michael Chas Sumner
  2. Steven B Torrisi
  3. Donna G Brickner
  4. Jason H Brickner  Is a corresponding author
  1. Northwestern University, United States
  2. Harvard University, United States

Abstract

Hundreds of genes interact with the yeast nuclear pore complex (NPC), localizing at the nuclear periphery and clustering with co-regulated genes. Dynamic tracking of peripheral genes shows that they cycle on and off the NPC and that interaction with the NPC slows their sub-diffusive movement. Furthermore, NPC-dependent inter-chromosomal clustering leads to coordinated movement of pairs of loci separated by hundreds of nanometers. We developed Fractional Brownian Motion simulations for chromosomal loci in the nucleoplasm and interacting with NPCs. These simulations predict the rate and nature of random sub-diffusion during repositioning from nucleoplasm to periphery and match measurements from two different experimental models, arguing that recruitment to the nuclear periphery is due to random sub-diffusion and transient capture by NPCs. Finally, the simulations do not lead to inter-chromosomal clustering or coordinated movement, suggesting that interaction with the NPC is necessary, but not sufficient, to cause clustering.

Data availability

All tracking data will be included as Source Data. All Scripts are publicly available from Github (https://github.com/MCnu/R_sim_scripts).

Article and author information

Author details

  1. Michael Chas Sumner

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Steven B Torrisi

    Physics, 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:" 0000-0002-4283-8077
  3. Donna G Brickner

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jason H Brickner

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    For correspondence
    j-brickner@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8019-3743

Funding

National Institutes of Health (R01 GM118712)

  • Michael Chas Sumner
  • Donna G Brickner
  • Jason H Brickner

National Institutes of Health (R35 GM136419)

  • Michael Chas Sumner
  • Donna G Brickner
  • Jason H Brickner

National Cancer Institute (U54 CA193419)

  • Michael Chas Sumner
  • Jason H Brickner

National Institutes of Health (T32 GM008061)

  • Michael Chas Sumner

Department of Energy, Labor and Economic Growth (DE-FG02-97ER25308)

  • Steven B Torrisi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Megan C King, Yale School of Medicine, United States

Publication history

  1. Received: January 5, 2021
  2. Accepted: May 17, 2021
  3. Accepted Manuscript published: May 18, 2021 (version 1)
  4. Version of Record published: June 11, 2021 (version 2)

Copyright

© 2021, Sumner 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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  1. Michael Chas Sumner
  2. Steven B Torrisi
  3. Donna G Brickner
  4. Jason H Brickner
(2021)
Random sub-diffusion and capture of genes by the nuclear pore reduces dynamics and coordinates interchromosomal movement
eLife 10:e66238.
https://doi.org/10.7554/eLife.66238

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