4.8 Article

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

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ELIFE
卷 10, 期 -, 页码 -

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ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.66238

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  1. National Institutes of Health [R01 GM118712, R35 GM136419, T32 GM008061]
  2. National Cancer Institute [U54 CA193419]
  3. Department of Energy, Labor and Economic Growth [DE-FG02-97ER25308]

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The study reveals that hundreds of genes interact with the yeast nuclear pore complex, localizing at the nuclear periphery. Interaction with the NPC slows down the movement of these genes and leads to coordinated movement of pairs of loci separated by hundreds of nanometers. Simulation predicts that recruitment to the nuclear periphery is due to random subdiffusion and transient capture by NPCs, but interaction with the NPC alone is not sufficient to cause clustering.
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 subdiffusive 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 subdiffusion 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.

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