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

Abstract
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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

Michael Chas Sumner

Department of Molecular Biosciences, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.
Steven B Torrisi

Physics, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4283-8077
Donna G Brickner

Department of Molecular Biosciences, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.
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.

"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.

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.