Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway

Abstract We explored how transcriptional noise propagates in gene‐regulatory pathways by studying the induction of two downstream genes by transcription factors c‐fos and c‐jun. They are produced for a brief period following serum stimulation of cells and then activate the promoters of their target...

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Main Authors: Khyati Shah, Sanjay Tyagi
Format: Article
Language:English
Published: Springer Nature 2013-09-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2013.45
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author Khyati Shah
Sanjay Tyagi
author_facet Khyati Shah
Sanjay Tyagi
author_sort Khyati Shah
collection DOAJ
description Abstract We explored how transcriptional noise propagates in gene‐regulatory pathways by studying the induction of two downstream genes by transcription factors c‐fos and c‐jun. They are produced for a brief period following serum stimulation of cells and then activate the promoters of their target genes by binding to them as heterodimers. We found that, even though they are coordinately expressed at the population level, in individual cells the expression of c‐fos and c‐jun is noisy and uncorrelated with each other. The expression of the downstream genes is also noisy, but there is little or no effect of the noise in the upstream genes on the expression of the downstream genes. The noise is not transmitted, because the number of heterodimers present in single cells is relatively invariant, and the induction of downstream genes is insensitive to the number of heterodimers in individual cells. Sequestration of promoters of the downstream genes within compact chromatin is a likely cause of this insensitivity. These barriers to the propagation and amplification of noise are likely to be commonplace in higher eukaryotes.
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spelling doaj-art-83f85c8be42a45d5906a09f372a427f92025-08-20T03:41:57ZengSpringer NatureMolecular Systems Biology1744-42922013-09-019111110.1038/msb.2013.45Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathwayKhyati Shah0Sanjay Tyagi1Public Health Research Institute, New Jersey Medical School, Rutgers UniversityPublic Health Research Institute, New Jersey Medical School, Rutgers UniversityAbstract We explored how transcriptional noise propagates in gene‐regulatory pathways by studying the induction of two downstream genes by transcription factors c‐fos and c‐jun. They are produced for a brief period following serum stimulation of cells and then activate the promoters of their target genes by binding to them as heterodimers. We found that, even though they are coordinately expressed at the population level, in individual cells the expression of c‐fos and c‐jun is noisy and uncorrelated with each other. The expression of the downstream genes is also noisy, but there is little or no effect of the noise in the upstream genes on the expression of the downstream genes. The noise is not transmitted, because the number of heterodimers present in single cells is relatively invariant, and the induction of downstream genes is insensitive to the number of heterodimers in individual cells. Sequestration of promoters of the downstream genes within compact chromatin is a likely cause of this insensitivity. These barriers to the propagation and amplification of noise are likely to be commonplace in higher eukaryotes.https://doi.org/10.1038/msb.2013.45cellular heterogeneitynoise in gene expressiontranscription
spellingShingle Khyati Shah
Sanjay Tyagi
Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway
Molecular Systems Biology
cellular heterogeneity
noise in gene expression
transcription
title Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway
title_full Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway
title_fullStr Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway
title_full_unstemmed Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway
title_short Barriers to transmission of transcriptional noise in a c‐fos c‐jun pathway
title_sort barriers to transmission of transcriptional noise in a c fos c jun pathway
topic cellular heterogeneity
noise in gene expression
transcription
url https://doi.org/10.1038/msb.2013.45
work_keys_str_mv AT khyatishah barrierstotransmissionoftranscriptionalnoiseinacfoscjunpathway
AT sanjaytyagi barrierstotransmissionoftranscriptionalnoiseinacfoscjunpathway