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Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences

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Origins of Transcriptional Transition : Balance between Upstream and Downstream Regulatory Gene Sequences. / Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram.

In: mBio, Vol. 6, No. 1, e02182-14, 2015.

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Sala, Adrien ; Shoaib, Muhammad ; Anufrieva, Olga ; Mutharasu, Gnanavel ; Yli-Harja, Olli ; Kandhavelu, Meenakshisundaram. / Origins of Transcriptional Transition : Balance between Upstream and Downstream Regulatory Gene Sequences. In: mBio. 2015 ; Vol. 6, No. 1.

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@article{9e2315ec8d734eb1aee61db29db373c9,
title = "Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences",
abstract = "By measuring individual mRNA production at the single-cell level, we investigated the lac promoter's transcriptional transition during cell growth phases. In exponential phase, variation in transition rates generates two mixed phenotypes, low and high numbers of mRNAs, by modulating their burst frequency and sizes. Independent activation of the regulatory-gene sequence does not produce bimodal populations at the mRNA level, but bimodal populations are produced when the regulatory gene is activated coordinately with the upstream and downstream region promoter sequence (URS and DRS, respectively). Time-lapse microscopy of mRNAs for lac and a variant lac promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between the URS and the DRS in transcriptional regulation determines population diversity.IMPORTANCE By measuring individual mRNA production at the single-cell level, we investigated the lac promoter transcriptional transition during cell growth phases. In exponential phase, variation in transition rate generates two mixed phenotypes producing low and high numbers of mRNAs by modulating the burst frequency and size. Independent activation of the regulatory gene sequence does not produce bimodal populations at the mRNA level, while it does when activated together through the coordination of upstream/downstream promoter sequences (URS/DRS). Time-lapse microscopy of mRNAs for lac and a lac variant promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between URS and DRS in transcription regulation is determining the population diversity.",
keywords = "SINGLE-MOLECULE EVENT, ESCHERICHIA-COLI, EXPRESSION, TIME, CELL, STOCHASTICITY, MECHANISMS, INITIATION, PROTEINS, DYNAMICS",
author = "Adrien Sala and Muhammad Shoaib and Olga Anufrieva and Gnanavel Mutharasu and Olli Yli-Harja and Meenakshisundaram Kandhavelu",
note = "AUX=sgn,{"}Shoaib, Muhammad{"} AUX=sgn,{"}Anufrieva, Olga{"}",
year = "2015",
doi = "10.1128/mBio.02182-14",
language = "English",
volume = "6",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "1",

}

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TY - JOUR

T1 - Origins of Transcriptional Transition

T2 - Balance between Upstream and Downstream Regulatory Gene Sequences

AU - Sala, Adrien

AU - Shoaib, Muhammad

AU - Anufrieva, Olga

AU - Mutharasu, Gnanavel

AU - Yli-Harja, Olli

AU - Kandhavelu, Meenakshisundaram

N1 - AUX=sgn,"Shoaib, Muhammad" AUX=sgn,"Anufrieva, Olga"

PY - 2015

Y1 - 2015

N2 - By measuring individual mRNA production at the single-cell level, we investigated the lac promoter's transcriptional transition during cell growth phases. In exponential phase, variation in transition rates generates two mixed phenotypes, low and high numbers of mRNAs, by modulating their burst frequency and sizes. Independent activation of the regulatory-gene sequence does not produce bimodal populations at the mRNA level, but bimodal populations are produced when the regulatory gene is activated coordinately with the upstream and downstream region promoter sequence (URS and DRS, respectively). Time-lapse microscopy of mRNAs for lac and a variant lac promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between the URS and the DRS in transcriptional regulation determines population diversity.IMPORTANCE By measuring individual mRNA production at the single-cell level, we investigated the lac promoter transcriptional transition during cell growth phases. In exponential phase, variation in transition rate generates two mixed phenotypes producing low and high numbers of mRNAs by modulating the burst frequency and size. Independent activation of the regulatory gene sequence does not produce bimodal populations at the mRNA level, while it does when activated together through the coordination of upstream/downstream promoter sequences (URS/DRS). Time-lapse microscopy of mRNAs for lac and a lac variant promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between URS and DRS in transcription regulation is determining the population diversity.

AB - By measuring individual mRNA production at the single-cell level, we investigated the lac promoter's transcriptional transition during cell growth phases. In exponential phase, variation in transition rates generates two mixed phenotypes, low and high numbers of mRNAs, by modulating their burst frequency and sizes. Independent activation of the regulatory-gene sequence does not produce bimodal populations at the mRNA level, but bimodal populations are produced when the regulatory gene is activated coordinately with the upstream and downstream region promoter sequence (URS and DRS, respectively). Time-lapse microscopy of mRNAs for lac and a variant lac promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between the URS and the DRS in transcriptional regulation determines population diversity.IMPORTANCE By measuring individual mRNA production at the single-cell level, we investigated the lac promoter transcriptional transition during cell growth phases. In exponential phase, variation in transition rate generates two mixed phenotypes producing low and high numbers of mRNAs by modulating the burst frequency and size. Independent activation of the regulatory gene sequence does not produce bimodal populations at the mRNA level, while it does when activated together through the coordination of upstream/downstream promoter sequences (URS/DRS). Time-lapse microscopy of mRNAs for lac and a lac variant promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between URS and DRS in transcription regulation is determining the population diversity.

KW - SINGLE-MOLECULE EVENT

KW - ESCHERICHIA-COLI

KW - EXPRESSION

KW - TIME

KW - CELL

KW - STOCHASTICITY

KW - MECHANISMS

KW - INITIATION

KW - PROTEINS

KW - DYNAMICS

U2 - 10.1128/mBio.02182-14

DO - 10.1128/mBio.02182-14

M3 - Article

VL - 6

JO - mBio

JF - mBio

SN - 2161-2129

IS - 1

M1 - e02182-14

ER -