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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.

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Related in: MedlinePlus

SIDD Profiles of the Genomic Regions Containing Genes (Operons) in the CysB Regulatory PathwayThe left panel shows a diagram for CysB regulatory pathway, according to the information provided in [54]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the CysB regulatory pathway. These profiles are aligned at their translation start sites.
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pcbi-0040017-g005: SIDD Profiles of the Genomic Regions Containing Genes (Operons) in the CysB Regulatory PathwayThe left panel shows a diagram for CysB regulatory pathway, according to the information provided in [54]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the CysB regulatory pathway. These profiles are aligned at their translation start sites.

Mentions: We next considered whether the other 15 LTTR genes and their targets also have similar SIDD properties at their 5′ upstream regions. We found that in the eight cases where the LTTR genes have the most highly destabilized upstream regions, the genes they regulate (where known) also have highly destabilized 5′ flanks. An example is provided by the cysB regulatory pathway, which positively controls cysteine biosynthesis in E. coli K12 [54]. The cysB gene whose product regulates this system is not linked to any of its many target genes, a group that includes the operons cysJIH, cysPTWA, and cysK. CysB positively regulates the expressions of these operons, and also directly regulates the expression of the tauABCD and ssuEADCB operons together with another LysR transcriptional regulator Cbl, whose gene is also controlled by CysB. Strikingly, every one of these operons, and the cysB gene itself, all have highly destabilized upstream regions. This is shown in Figure 5, which displays the SIDD profiles of these operons and their upstream regions aligned at their translation start sites.


Superhelical destabilization in regulatory regions of stress response genes.

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

SIDD Profiles of the Genomic Regions Containing Genes (Operons) in the CysB Regulatory PathwayThe left panel shows a diagram for CysB regulatory pathway, according to the information provided in [54]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the CysB regulatory pathway. These profiles are aligned at their translation start sites.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0040017-g005: SIDD Profiles of the Genomic Regions Containing Genes (Operons) in the CysB Regulatory PathwayThe left panel shows a diagram for CysB regulatory pathway, according to the information provided in [54]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the CysB regulatory pathway. These profiles are aligned at their translation start sites.
Mentions: We next considered whether the other 15 LTTR genes and their targets also have similar SIDD properties at their 5′ upstream regions. We found that in the eight cases where the LTTR genes have the most highly destabilized upstream regions, the genes they regulate (where known) also have highly destabilized 5′ flanks. An example is provided by the cysB regulatory pathway, which positively controls cysteine biosynthesis in E. coli K12 [54]. The cysB gene whose product regulates this system is not linked to any of its many target genes, a group that includes the operons cysJIH, cysPTWA, and cysK. CysB positively regulates the expressions of these operons, and also directly regulates the expression of the tauABCD and ssuEADCB operons together with another LysR transcriptional regulator Cbl, whose gene is also controlled by CysB. Strikingly, every one of these operons, and the cysB gene itself, all have highly destabilized upstream regions. This is shown in Figure 5, which displays the SIDD profiles of these operons and their upstream regions aligned at their translation start sites.

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