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 b...

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Autores principales:	Adrien Sala, Muhammad Shoaib, Olga Anufrieva, Gnanavel Mutharasu, Olli Yli-Harja, Meenakshisundaram Kandhavelu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/abb6d2e7498d4d989e193838b8ef6b47
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spelling	oai:doaj.org-article:abb6d2e7498d4d989e193838b8ef6b472021-11-15T15:41:18ZOrigins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences10.1128/mBio.02182-142150-7511https://doaj.org/article/abb6d2e7498d4d989e193838b8ef6b472015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02182-14https://doaj.org/toc/2150-7511ABSTRACT 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.Adrien SalaMuhammad ShoaibOlga AnufrievaGnanavel MutharasuOlli Yli-HarjaMeenakshisundaram KandhaveluAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Adrien Sala Muhammad Shoaib Olga Anufrieva Gnanavel Mutharasu Olli Yli-Harja Meenakshisundaram Kandhavelu Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
description	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.
format	article
author	Adrien Sala Muhammad Shoaib Olga Anufrieva Gnanavel Mutharasu Olli Yli-Harja Meenakshisundaram Kandhavelu
author_facet	Adrien Sala Muhammad Shoaib Olga Anufrieva Gnanavel Mutharasu Olli Yli-Harja Meenakshisundaram Kandhavelu
author_sort	Adrien Sala
title	Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
title_short	Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
title_full	Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
title_fullStr	Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
title_full_unstemmed	Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
title_sort	origins of transcriptional transition: balance between upstream and downstream regulatory gene sequences
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/abb6d2e7498d4d989e193838b8ef6b47
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_version_	1718427722146906112

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

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