Limits...
Superhelical destabilization in regulatory regions of stress response genes.

Wang H, Benham CJ - PLoS Comput. Biol. (2008)

Bottom Line: We observe this statistically significant association of SIDD sites with upstream regions of genes functioning in transcription in 38 of 43 genomes of free-living bacteria, but in only four of 18 genomes of endosymbionts or obligate parasitic bacteria.These results suggest that strong SIDD sites 5' to participating genes may be involved in transcriptional responses to environmental changes, which are known to transiently alter superhelicity.We propose that these SIDD sites are active and necessary participants in superhelically mediated regulatory mechanisms governing changes in the global pattern of gene expression in prokaryotes in response to physiological or environmental changes.

View Article: PubMed Central - PubMed

Affiliation: UC Davis Genome Center, University of California Davis, Davis, California, United States of America.

ABSTRACT
Stress-induced DNA duplex destabilization (SIDD) analysis exploits the known structural and energetic properties of DNA to predict sites that are susceptible to strand separation under negative superhelical stress. When this approach was used to calculate the SIDD profile of the entire Escherichia coli K12 genome, it was found that strongly destabilized sites occur preferentially in intergenic regions that are either known or inferred to contain promoters, but rarely occur in coding regions. Here, we investigate whether the genes grouped in different functional categories have characteristic SIDD properties in their upstream flanks. We report that strong SIDD sites in the E. coli K12 genome are statistically significantly overrepresented in the upstream regions of genes encoding transcriptional regulators. In particular, the upstream regions of genes that directly respond to physiological and environmental stimuli are more destabilized than are those regions of genes that are not involved in these responses. Moreover, if a pathway is controlled by a transcriptional regulator whose gene has a destabilized 5' flank, then the genes (operons) in that pathway also usually contain strongly destabilized SIDD sites in their 5' flanks. We observe this statistically significant association of SIDD sites with upstream regions of genes functioning in transcription in 38 of 43 genomes of free-living bacteria, but in only four of 18 genomes of endosymbionts or obligate parasitic bacteria. These results suggest that strong SIDD sites 5' to participating genes may be involved in transcriptional responses to environmental changes, which are known to transiently alter superhelicity. We propose that these SIDD sites are active and necessary participants in superhelically mediated regulatory mechanisms governing changes in the global pattern of gene expression in prokaryotes in response to physiological or environmental changes.

Show MeSH

Related in: MedlinePlus

Proposed Model of SIDD-Mediated Transcriptional RegulationStrong SIDD sites are proposed to be important regulatory elements for global gene expression in response to environmental or physiological stresses.doi: 0.1371/journal.pcbi.0040017.g007
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211533&req=5

pcbi-0040017-g007: Proposed Model of SIDD-Mediated Transcriptional RegulationStrong SIDD sites are proposed to be important regulatory elements for global gene expression in response to environmental or physiological stresses.doi: 0.1371/journal.pcbi.0040017.g007

Mentions: Figure 7 presents a diagram of a model for the cascade of events consequent on a physiological or environmental change. When a bacterium experiences such a change, its transcriptional program must be modified in response. Two interacting components of the regulatory machinery are considered here—transcriptional regulators and DNA supercoiling. The changed levels of DNA supercoiling that result from an environmental or physiological transition, acting in concert with protein binding events, either activate or repress the expressions of specific sets of genes which are involved in adapting to these changes. In some mechanisms, these components may influence the response to environmental or physiological changes through their effects on the duplex stability at strong SIDD sites. This is possible because changes in DNA supercoiling alter the torsional stresses that drive DNA duplex destabilization, which will be concentrated at the strong SIDD sites. Acting in concert with transcriptional regulators, strong SIDD sites may serve as switches to tune the expression of certain sets of genes, operons, or pathways. In this way, changes in the activities of global regulators, and particularly the “first responders,” together with supercoiling-induced duplex destabilization events, provide a large number of possible mechanisms by which a bacterium may adjust its physiological activities (metabolism) to adapt to changes in its living environment or physiological state.


Superhelical destabilization in regulatory regions of stress response genes.

Wang H, Benham CJ - PLoS Comput. Biol. (2008)

Proposed Model of SIDD-Mediated Transcriptional RegulationStrong SIDD sites are proposed to be important regulatory elements for global gene expression in response to environmental or physiological stresses.doi: 0.1371/journal.pcbi.0040017.g007
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211533&req=5

pcbi-0040017-g007: Proposed Model of SIDD-Mediated Transcriptional RegulationStrong SIDD sites are proposed to be important regulatory elements for global gene expression in response to environmental or physiological stresses.doi: 0.1371/journal.pcbi.0040017.g007
Mentions: Figure 7 presents a diagram of a model for the cascade of events consequent on a physiological or environmental change. When a bacterium experiences such a change, its transcriptional program must be modified in response. Two interacting components of the regulatory machinery are considered here—transcriptional regulators and DNA supercoiling. The changed levels of DNA supercoiling that result from an environmental or physiological transition, acting in concert with protein binding events, either activate or repress the expressions of specific sets of genes which are involved in adapting to these changes. In some mechanisms, these components may influence the response to environmental or physiological changes through their effects on the duplex stability at strong SIDD sites. This is possible because changes in DNA supercoiling alter the torsional stresses that drive DNA duplex destabilization, which will be concentrated at the strong SIDD sites. Acting in concert with transcriptional regulators, strong SIDD sites may serve as switches to tune the expression of certain sets of genes, operons, or pathways. In this way, changes in the activities of global regulators, and particularly the “first responders,” together with supercoiling-induced duplex destabilization events, provide a large number of possible mechanisms by which a bacterium may adjust its physiological activities (metabolism) to adapt to changes in its living environment or physiological state.

Bottom Line: We observe this statistically significant association of SIDD sites with upstream regions of genes functioning in transcription in 38 of 43 genomes of free-living bacteria, but in only four of 18 genomes of endosymbionts or obligate parasitic bacteria.These results suggest that strong SIDD sites 5' to participating genes may be involved in transcriptional responses to environmental changes, which are known to transiently alter superhelicity.We propose that these SIDD sites are active and necessary participants in superhelically mediated regulatory mechanisms governing changes in the global pattern of gene expression in prokaryotes in response to physiological or environmental changes.

View Article: PubMed Central - PubMed

Affiliation: UC Davis Genome Center, University of California Davis, Davis, California, United States of America.

ABSTRACT
Stress-induced DNA duplex destabilization (SIDD) analysis exploits the known structural and energetic properties of DNA to predict sites that are susceptible to strand separation under negative superhelical stress. When this approach was used to calculate the SIDD profile of the entire Escherichia coli K12 genome, it was found that strongly destabilized sites occur preferentially in intergenic regions that are either known or inferred to contain promoters, but rarely occur in coding regions. Here, we investigate whether the genes grouped in different functional categories have characteristic SIDD properties in their upstream flanks. We report that strong SIDD sites in the E. coli K12 genome are statistically significantly overrepresented in the upstream regions of genes encoding transcriptional regulators. In particular, the upstream regions of genes that directly respond to physiological and environmental stimuli are more destabilized than are those regions of genes that are not involved in these responses. Moreover, if a pathway is controlled by a transcriptional regulator whose gene has a destabilized 5' flank, then the genes (operons) in that pathway also usually contain strongly destabilized SIDD sites in their 5' flanks. We observe this statistically significant association of SIDD sites with upstream regions of genes functioning in transcription in 38 of 43 genomes of free-living bacteria, but in only four of 18 genomes of endosymbionts or obligate parasitic bacteria. These results suggest that strong SIDD sites 5' to participating genes may be involved in transcriptional responses to environmental changes, which are known to transiently alter superhelicity. We propose that these SIDD sites are active and necessary participants in superhelically mediated regulatory mechanisms governing changes in the global pattern of gene expression in prokaryotes in response to physiological or environmental changes.

Show MeSH
Related in: MedlinePlus