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Slow, stochastic transgene repression with properties of a timer
BACKGROUND: When gene expression varies unpredictably between genetically identical organisms, this is sometimes ascribed as stochastic. With the prevalence of retroviral vectors, stochastic repression is often observed and can complicate the interpretation of outcomes. But it may also faithfully re...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779533/ https://www.ncbi.nlm.nih.gov/pubmed/16764729 http://dx.doi.org/10.1186/gb-2006-7-6-r47 |
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author | Wang, Clifford L Yang, Desirée C Wabl, Matthias |
author_facet | Wang, Clifford L Yang, Desirée C Wabl, Matthias |
author_sort | Wang, Clifford L |
collection | PubMed |
description | BACKGROUND: When gene expression varies unpredictably between genetically identical organisms, this is sometimes ascribed as stochastic. With the prevalence of retroviral vectors, stochastic repression is often observed and can complicate the interpretation of outcomes. But it may also faithfully reflect characteristics of sites in the genome. RESULTS: We created and identified several cell clones in which, within a given cell, retroviral transcription of a transgene was repressed heritably and essentially irreversibly. This repression was relatively slow; total repression in all cells took months. We observed the dynamics of repression and found that they were ergodic, that is, tending with a probability to a final state independent of previous conditions. Different positions of the transgene in the genome demonstrated different dynamics. At a position on mouse chromosome 9, repression abided by near perfect first-order kinetics and was highly reproducible, even under conditions where the number of cell generations per day varied. CONCLUSION: We propose that such a cell division independent 'off' mechanism could play a role in endogenous gene expression, potentially providing an epigenetically based timer for extended periods. |
format | Text |
id | pubmed-1779533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-17795332007-01-19 Slow, stochastic transgene repression with properties of a timer Wang, Clifford L Yang, Desirée C Wabl, Matthias Genome Biol Research BACKGROUND: When gene expression varies unpredictably between genetically identical organisms, this is sometimes ascribed as stochastic. With the prevalence of retroviral vectors, stochastic repression is often observed and can complicate the interpretation of outcomes. But it may also faithfully reflect characteristics of sites in the genome. RESULTS: We created and identified several cell clones in which, within a given cell, retroviral transcription of a transgene was repressed heritably and essentially irreversibly. This repression was relatively slow; total repression in all cells took months. We observed the dynamics of repression and found that they were ergodic, that is, tending with a probability to a final state independent of previous conditions. Different positions of the transgene in the genome demonstrated different dynamics. At a position on mouse chromosome 9, repression abided by near perfect first-order kinetics and was highly reproducible, even under conditions where the number of cell generations per day varied. CONCLUSION: We propose that such a cell division independent 'off' mechanism could play a role in endogenous gene expression, potentially providing an epigenetically based timer for extended periods. BioMed Central 2006 2006-06-09 /pmc/articles/PMC1779533/ /pubmed/16764729 http://dx.doi.org/10.1186/gb-2006-7-6-r47 Text en Copyright © 2006 Wang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Wang, Clifford L Yang, Desirée C Wabl, Matthias Slow, stochastic transgene repression with properties of a timer |
title | Slow, stochastic transgene repression with properties of a timer |
title_full | Slow, stochastic transgene repression with properties of a timer |
title_fullStr | Slow, stochastic transgene repression with properties of a timer |
title_full_unstemmed | Slow, stochastic transgene repression with properties of a timer |
title_short | Slow, stochastic transgene repression with properties of a timer |
title_sort | slow, stochastic transgene repression with properties of a timer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779533/ https://www.ncbi.nlm.nih.gov/pubmed/16764729 http://dx.doi.org/10.1186/gb-2006-7-6-r47 |
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