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Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability.

ABSTRACT: In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional ? factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given ? factor. In contrast, different ? factors have different affinities for the RNAP core. As a consequence, the concentration of alternate ? factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different ?/anti-? controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these ?/anti-? post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli.

SUBMITTER: Trevino-Quintanilla LG

PROVIDER: S-EPMC3861889 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other

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Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability.

Treviño-Quintanilla Luis Gerardo LG Freyre-González Julio Augusto JA Martínez-Flores Irma I

Current genomics 20130901 6

In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation i ...[more]

PMID: 24396271

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Project description:Enterohemorrhagic Escherichia coli (EHEC) is dependent on acid resistance for gastric passage and low oral infectious dose, and the locus of enterocyte effacement (LEE) for intestinal colonization. Mutation of rpoN, encoding sigma factor N (σ(N)), dramatically alters the growth-phase dependent regulation of both acid resistance and the LEE. This study reports on the determinants of σ(N)-directed acid resistance and LEE expression, and the underlying mechanism attributable to this phenotype. Glutamate-dependent acid resistance (GDAR) in TW14359ΔrpoN correlated with increased expression of the gadX-gadW regulatory circuit during exponential growth, whereas upregulation of arginine-dependent acid resistance (ADAR) genes adiA and adiC in TW14359ΔrpoN did not confer acid resistance by the ADAR mechanism. LEE regulatory (ler), structural (espA and cesT) and effector (tir) genes were downregulated in TW14359ΔrpoN, and mutation of rpoS encoding sigma factor 38 (σ(S)) in TW14359ΔrpoN restored acid resistance and LEE genes to WT levels. Stability, but not the absolute level, of σ(S) was increased in TW14359ΔrpoN; however, increased stability was not solely attributable to the GDAR and LEE expression phenotype. Complementation of TW14359ΔrpoN with a σ(N) allele that binds RNA polymerase (RNAP) but not DNA, did not restore WT levels of σ(S) stability, gadE, ler or GDAR, indicating a dependence on transcription from a σ(N) promoter(s) and not RNAP competition for the phenotype. Among a library of σ(N) enhancer binding protein mutants, only TW14359ΔntrC, inactivated for nitrogen regulatory protein NtrC, phenocopied TW14359ΔrpoN for σ(S) stability, GDAR and ler expression. The results of this study suggest that during exponential growth, NtrC-σ(N) regulate GDAR and LEE expression through downregulation of σ(S) at the post-translational level; likely by altering σ(S) stability or activity. The regulatory interplay between NtrC, other EBPs, and σ(N)-σ(S), represents a mechanism by which EHEC can coordinate GDAR, LEE expression and other cellular functions, with nitrogen availability and physiologic stimuli.

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Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability.

Publications

Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability.

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