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Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?

One of the functions of the cell nucleus is to help regulate gene expression by controlling molecular traffic across the nuclear envelope. Here we investigate, via stochastic simulation, what effects, if any, does segregation of a system into the nuclear and cytoplasmic compartments have on the stoc...

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Autores principales: Albert, Jaroslav, Rooman, Marianne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520485/
https://www.ncbi.nlm.nih.gov/pubmed/26226505
http://dx.doi.org/10.1371/journal.pone.0134239
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author Albert, Jaroslav
Rooman, Marianne
author_facet Albert, Jaroslav
Rooman, Marianne
author_sort Albert, Jaroslav
collection PubMed
description One of the functions of the cell nucleus is to help regulate gene expression by controlling molecular traffic across the nuclear envelope. Here we investigate, via stochastic simulation, what effects, if any, does segregation of a system into the nuclear and cytoplasmic compartments have on the stochastic properties of a motif with a negative feedback. One of the effects of the nuclear barrier is to delay the nuclear protein concentration, allowing it to behave in a switch-like manner. We found that this delay, defined as the time for the nuclear protein concentration to reach a certain threshold, has an extremely narrow distribution. To show this, we considered two models. In the first one, the proteins could diffuse freely from cytoplasm to nucleus (simple model); and in the second one, the proteins required assistance from a special class of proteins called importins. For each model, we generated fifty parameter sets, chosen such that the temporal profiles they effectuated were very similar, and whose average threshold time was approximately 150 minutes. The standard deviation of the threshold times computed over one hundred realizations were found to be between 1.8 and 7.16 minutes across both models. To see whether a genetic motif in a prokaryotic cell can achieve this degree of precision, we also simulated five variations on the coherent feed-forward motif (CFFM), three of which contained a negative feedback. We found that the performance of these motifs was nowhere near as impressive as the one found in the eukaryotic cell; the best standard deviation was 6.6 minutes. We argue that the significance of these results, the fact and necessity of spatio-temporal precision in the developmental stages of eukaryotes, and the absence of such a precision in prokaryotes, all suggest that the nucleus has evolved, in part, under the selective pressure to achieve highly predictable phenotypes.
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spelling pubmed-45204852015-08-06 Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning? Albert, Jaroslav Rooman, Marianne PLoS One Research Article One of the functions of the cell nucleus is to help regulate gene expression by controlling molecular traffic across the nuclear envelope. Here we investigate, via stochastic simulation, what effects, if any, does segregation of a system into the nuclear and cytoplasmic compartments have on the stochastic properties of a motif with a negative feedback. One of the effects of the nuclear barrier is to delay the nuclear protein concentration, allowing it to behave in a switch-like manner. We found that this delay, defined as the time for the nuclear protein concentration to reach a certain threshold, has an extremely narrow distribution. To show this, we considered two models. In the first one, the proteins could diffuse freely from cytoplasm to nucleus (simple model); and in the second one, the proteins required assistance from a special class of proteins called importins. For each model, we generated fifty parameter sets, chosen such that the temporal profiles they effectuated were very similar, and whose average threshold time was approximately 150 minutes. The standard deviation of the threshold times computed over one hundred realizations were found to be between 1.8 and 7.16 minutes across both models. To see whether a genetic motif in a prokaryotic cell can achieve this degree of precision, we also simulated five variations on the coherent feed-forward motif (CFFM), three of which contained a negative feedback. We found that the performance of these motifs was nowhere near as impressive as the one found in the eukaryotic cell; the best standard deviation was 6.6 minutes. We argue that the significance of these results, the fact and necessity of spatio-temporal precision in the developmental stages of eukaryotes, and the absence of such a precision in prokaryotes, all suggest that the nucleus has evolved, in part, under the selective pressure to achieve highly predictable phenotypes. Public Library of Science 2015-07-30 /pmc/articles/PMC4520485/ /pubmed/26226505 http://dx.doi.org/10.1371/journal.pone.0134239 Text en © 2015 Albert, Rooman http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Albert, Jaroslav
Rooman, Marianne
Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?
title Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?
title_full Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?
title_fullStr Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?
title_full_unstemmed Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?
title_short Is the Cell Nucleus a Necessary Component in Precise Temporal Patterning?
title_sort is the cell nucleus a necessary component in precise temporal patterning?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520485/
https://www.ncbi.nlm.nih.gov/pubmed/26226505
http://dx.doi.org/10.1371/journal.pone.0134239
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