Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics

ABSTRACT Understanding cellular responses to environmental stimuli requires not only the knowledge of specific regulatory components but also the quantitative characterization of the magnitude and timing of regulatory events. The two-component system is one of the major prokaryotic signaling schemes...

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Autores principales:	Rong Gao, Ann M. Stock
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e199c81435704fd9b26799e252aaa680
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spelling	oai:doaj.org-article:e199c81435704fd9b26799e252aaa6802021-11-15T15:49:03ZTemporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics10.1128/mBio.00686-152150-7511https://doaj.org/article/e199c81435704fd9b26799e252aaa6802015-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00686-15https://doaj.org/toc/2150-7511ABSTRACT Understanding cellular responses to environmental stimuli requires not only the knowledge of specific regulatory components but also the quantitative characterization of the magnitude and timing of regulatory events. The two-component system is one of the major prokaryotic signaling schemes and is the focus of extensive interest in quantitative modeling and investigation of signaling dynamics. Here we report how the binding affinity of the PhoB two-component response regulator (RR) to target promoters impacts the level and timing of expression of PhoB-regulated genes. Information content has often been used to assess the degree of conservation for transcription factor (TF)-binding sites. We show that increasing the information content of PhoB-binding sites in designed phoA promoters increased the binding affinity and that the binding affinity and concentration of phosphorylated PhoB (PhoB~P) together dictate the level and timing of expression of phoA promoter variants. For various PhoB-regulated promoters with distinct promoter architectures, expression levels appear not to be correlated with TF-binding affinities, in contrast to the intuitive and oversimplified assumption that promoters with higher affinity for a TF tend to have higher expression levels. However, the expression timing of the core set of PhoB-regulated genes correlates well with the binding affinity of PhoB~P to individual promoters and the temporal hierarchy of gene expression appears to be related to the function of gene products during the phosphate starvation response. Modulation of the information content and binding affinity of TF-binding sites may be a common strategy for temporal programming of the expression profile of RR-regulated genes. IMPORTANCE A single TF often orchestrates the expression of multiple genes in response to environmental stimuli. It is not clear how different TF-binding sites within the regulon dictate the expression profile. Our studies of Escherichia coli PhoB, a response regulator that controls expression of a core set of phosphate assimilation genes in response to phosphate starvation, showed that expression levels of PhoB-regulated genes are under sophisticated control and do not follow a simple correlation with the binding affinity of PhoB~P to individual promoters. However, the expression timing correlates with the PhoB-binding affinity and gene functions. Genes involved in direct Pi uptake contain high-affinity sites and are transcribed earlier than genes involved in phosphorus scavenging. This illustrates an elaborate mechanism of temporally programmed gene expression, even for nondevelopmental pathways.Rong GaoAnn M. StockAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 3 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Rong Gao Ann M. Stock Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics
description	ABSTRACT Understanding cellular responses to environmental stimuli requires not only the knowledge of specific regulatory components but also the quantitative characterization of the magnitude and timing of regulatory events. The two-component system is one of the major prokaryotic signaling schemes and is the focus of extensive interest in quantitative modeling and investigation of signaling dynamics. Here we report how the binding affinity of the PhoB two-component response regulator (RR) to target promoters impacts the level and timing of expression of PhoB-regulated genes. Information content has often been used to assess the degree of conservation for transcription factor (TF)-binding sites. We show that increasing the information content of PhoB-binding sites in designed phoA promoters increased the binding affinity and that the binding affinity and concentration of phosphorylated PhoB (PhoB~P) together dictate the level and timing of expression of phoA promoter variants. For various PhoB-regulated promoters with distinct promoter architectures, expression levels appear not to be correlated with TF-binding affinities, in contrast to the intuitive and oversimplified assumption that promoters with higher affinity for a TF tend to have higher expression levels. However, the expression timing of the core set of PhoB-regulated genes correlates well with the binding affinity of PhoB~P to individual promoters and the temporal hierarchy of gene expression appears to be related to the function of gene products during the phosphate starvation response. Modulation of the information content and binding affinity of TF-binding sites may be a common strategy for temporal programming of the expression profile of RR-regulated genes. IMPORTANCE A single TF often orchestrates the expression of multiple genes in response to environmental stimuli. It is not clear how different TF-binding sites within the regulon dictate the expression profile. Our studies of Escherichia coli PhoB, a response regulator that controls expression of a core set of phosphate assimilation genes in response to phosphate starvation, showed that expression levels of PhoB-regulated genes are under sophisticated control and do not follow a simple correlation with the binding affinity of PhoB~P to individual promoters. However, the expression timing correlates with the PhoB-binding affinity and gene functions. Genes involved in direct Pi uptake contain high-affinity sites and are transcribed earlier than genes involved in phosphorus scavenging. This illustrates an elaborate mechanism of temporally programmed gene expression, even for nondevelopmental pathways.
format	article
author	Rong Gao Ann M. Stock
author_facet	Rong Gao Ann M. Stock
author_sort	Rong Gao
title	Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics
title_short	Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics
title_full	Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics
title_fullStr	Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics
title_full_unstemmed	Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics
title_sort	temporal hierarchy of gene expression mediated by transcription factor binding affinity and activation dynamics
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/e199c81435704fd9b26799e252aaa680
work_keys_str_mv	AT ronggao temporalhierarchyofgeneexpressionmediatedbytranscriptionfactorbindingaffinityandactivationdynamics AT annmstock temporalhierarchyofgeneexpressionmediatedbytranscriptionfactorbindingaffinityandactivationdynamics
_version_	1718427492358815744

Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics

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