Structure of silent transcription intervals and noise characteristics of mammalian genes
Abstract Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time‐lapse recordings in mouse ce...
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20156257 |
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| author | Benjamin Zoller Damien Nicolas Nacho Molina Felix Naef |
| author_facet | Benjamin Zoller Damien Nicolas Nacho Molina Felix Naef |
| author_sort | Benjamin Zoller |
| collection | DOAJ |
| description | Abstract Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time‐lapse recordings in mouse cells to identify minimal models of promoter cycles, which inform on the number and durations of rate‐limiting steps responsible for refractory periods. The structure of promoter cycles is gene specific and independent of genomic location. Typically, five rate‐limiting steps underlie the silent periods of endogenous promoters, while minimal synthetic promoters exhibit only one. Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two‐state promoter cycles. Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome‐wide in mammals, as revealed by single‐cell RNA‐seq. These findings have implications for basic transcription biology and shed light on interpreting single‐cell RNA‐counting experiments. |
| format | Article |
| id | doaj-art-c45ca63a29b840e38a4c119df92bb6e6 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2015-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c45ca63a29b840e38a4c119df92bb6e62025-08-20T02:11:55ZengSpringer NatureMolecular Systems Biology1744-42922015-07-0111711510.15252/msb.20156257Structure of silent transcription intervals and noise characteristics of mammalian genesBenjamin Zoller0Damien Nicolas1Nacho Molina2Felix Naef3The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneThe Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneThe Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneThe Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneAbstract Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time‐lapse recordings in mouse cells to identify minimal models of promoter cycles, which inform on the number and durations of rate‐limiting steps responsible for refractory periods. The structure of promoter cycles is gene specific and independent of genomic location. Typically, five rate‐limiting steps underlie the silent periods of endogenous promoters, while minimal synthetic promoters exhibit only one. Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two‐state promoter cycles. Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome‐wide in mammals, as revealed by single‐cell RNA‐seq. These findings have implications for basic transcription biology and shed light on interpreting single‐cell RNA‐counting experiments.https://doi.org/10.15252/msb.20156257noise in mRNA countspromoter cyclesingle‐cell time‐lapse analysisstochastic gene expressiontranscriptional bursting |
| spellingShingle | Benjamin Zoller Damien Nicolas Nacho Molina Felix Naef Structure of silent transcription intervals and noise characteristics of mammalian genes Molecular Systems Biology noise in mRNA counts promoter cycle single‐cell time‐lapse analysis stochastic gene expression transcriptional bursting |
| title | Structure of silent transcription intervals and noise characteristics of mammalian genes |
| title_full | Structure of silent transcription intervals and noise characteristics of mammalian genes |
| title_fullStr | Structure of silent transcription intervals and noise characteristics of mammalian genes |
| title_full_unstemmed | Structure of silent transcription intervals and noise characteristics of mammalian genes |
| title_short | Structure of silent transcription intervals and noise characteristics of mammalian genes |
| title_sort | structure of silent transcription intervals and noise characteristics of mammalian genes |
| topic | noise in mRNA counts promoter cycle single‐cell time‐lapse analysis stochastic gene expression transcriptional bursting |
| url | https://doi.org/10.15252/msb.20156257 |
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