Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior

ABSTRACT Exploiting mechanisms of utilizing the sugar d-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the d-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies reveale...

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Autores principales:	Sang Jun Lee, Andrei Trostel, Sankar Adhya
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bcf3720b540f45f8866efd71ba44c4dd
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spelling	oai:doaj.org-article:bcf3720b540f45f8866efd71ba44c4dd2021-11-15T15:45:09ZMetabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior10.1128/mBio.00972-132150-7511https://doaj.org/article/bcf3720b540f45f8866efd71ba44c4dd2014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00972-13https://doaj.org/toc/2150-7511ABSTRACT Exploiting mechanisms of utilizing the sugar d-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the d-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies revealed both metabolic network changes far from the d-galactose pathway and changes in the global gene regulatory network. The concentration change of a critical intermediate disturbs the equilibrium state, generating a ripple effect through several metabolic pathways that ends up signaling up- or downregulation of specific sets of genes in a programmed manner to cope with the imbalance. Such long-range effects on metabolites and genetic regulatory mechanisms not only may be a common feature in bacteria but very likely operate during cellular development and differentiation in higher organisms as well as in disease cells, like cancer cells. IMPORTANCE Metabolite accumulation can create adverse intracellular conditions that are relieved by compensatory immediate changes of metabolite pools and later changes of transcript levels. It has been known that gene expression is normally regulated by added catabolic substrates (induction) or anabolic end products (repression). It is becoming apparent now that change in the concentration of metabolic intermediates also plays a critical role in genetic regulatory networks for metabolic homeostasis. Our study provides new insight into how metabolite pool changes transduce signals to global gene regulatory networks.Sang Jun LeeAndrei TrostelSankar AdhyaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Sang Jun Lee Andrei Trostel Sankar Adhya Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior
description	ABSTRACT Exploiting mechanisms of utilizing the sugar d-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the d-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies revealed both metabolic network changes far from the d-galactose pathway and changes in the global gene regulatory network. The concentration change of a critical intermediate disturbs the equilibrium state, generating a ripple effect through several metabolic pathways that ends up signaling up- or downregulation of specific sets of genes in a programmed manner to cope with the imbalance. Such long-range effects on metabolites and genetic regulatory mechanisms not only may be a common feature in bacteria but very likely operate during cellular development and differentiation in higher organisms as well as in disease cells, like cancer cells. IMPORTANCE Metabolite accumulation can create adverse intracellular conditions that are relieved by compensatory immediate changes of metabolite pools and later changes of transcript levels. It has been known that gene expression is normally regulated by added catabolic substrates (induction) or anabolic end products (repression). It is becoming apparent now that change in the concentration of metabolic intermediates also plays a critical role in genetic regulatory networks for metabolic homeostasis. Our study provides new insight into how metabolite pool changes transduce signals to global gene regulatory networks.
format	article
author	Sang Jun Lee Andrei Trostel Sankar Adhya
author_facet	Sang Jun Lee Andrei Trostel Sankar Adhya
author_sort	Sang Jun Lee
title	Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior
title_short	Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior
title_full	Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior
title_fullStr	Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior
title_full_unstemmed	Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior
title_sort	metabolite changes signal genetic regulatory mechanisms for robust cell behavior
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/bcf3720b540f45f8866efd71ba44c4dd
work_keys_str_mv	AT sangjunlee metabolitechangessignalgeneticregulatorymechanismsforrobustcellbehavior AT andreitrostel metabolitechangessignalgeneticregulatorymechanismsforrobustcellbehavior AT sankaradhya metabolitechangessignalgeneticregulatorymechanismsforrobustcellbehavior
_version_	1718427608304058368

Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior

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