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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 (Openons) in Nitrogen Metabolism Regulatory PathwayThe left panel shows a diagram for nitrogen metabolism regulatory pathway, redrawn with permission from [56]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the nitrogen metabolism regulatory pathway. These profiles are aligned at their translation start sites.
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pcbi-0040017-g006: SIDD Profiles of the Genomic Regions Containing Genes (Openons) in Nitrogen Metabolism Regulatory PathwayThe left panel shows a diagram for nitrogen metabolism regulatory pathway, redrawn with permission from [56]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the nitrogen metabolism regulatory pathway. These profiles are aligned at their translation start sites.

Mentions: As described above, the upstream flanks of the first genes in these operons are statistically significantly enriched in strongest SIDD (i.e., SIDD0) sites at the p < 0.01 level. In five of the six cases where the two genes comprising a system are separated, both genes in the pair are destabilized in their 5′ flanks to similar extents. Two representative examples are NarP/NarQ and NarL/NarX. These systems regulate anaerobic gene expression when nitrate and/or nitrite are available [55]. The narX and narL genes form an operon narXL, while the narP and narQ genes are separated by about 300 kbp in the genome. There are SIDD0 sites located in the upstream regulatory regions of both the narQ and narP genes, as well as in that of the narX gene, the first gene in the narXL operon. These systems are known to regulate four transcriptional units, the narK gene and the narGHJI, fdnGHI, and frdABCD operons [56]. The SIDD profiles of these genes and operons are shown in Figure 6. The upstream regions of six of these seven transcriptional units are strongly destabilized, the exception being fdnGHI. In contrast, the upstream regions of internal genes in all these operons are substantially more stable.


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 (Openons) in Nitrogen Metabolism Regulatory PathwayThe left panel shows a diagram for nitrogen metabolism regulatory pathway, redrawn with permission from [56]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the nitrogen metabolism 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-g006: SIDD Profiles of the Genomic Regions Containing Genes (Openons) in Nitrogen Metabolism Regulatory PathwayThe left panel shows a diagram for nitrogen metabolism regulatory pathway, redrawn with permission from [56]. The right panel shows the SIDD profiles for the operons encoding the genes for the proteins in the nitrogen metabolism regulatory pathway. These profiles are aligned at their translation start sites.
Mentions: As described above, the upstream flanks of the first genes in these operons are statistically significantly enriched in strongest SIDD (i.e., SIDD0) sites at the p < 0.01 level. In five of the six cases where the two genes comprising a system are separated, both genes in the pair are destabilized in their 5′ flanks to similar extents. Two representative examples are NarP/NarQ and NarL/NarX. These systems regulate anaerobic gene expression when nitrate and/or nitrite are available [55]. The narX and narL genes form an operon narXL, while the narP and narQ genes are separated by about 300 kbp in the genome. There are SIDD0 sites located in the upstream regulatory regions of both the narQ and narP genes, as well as in that of the narX gene, the first gene in the narXL operon. These systems are known to regulate four transcriptional units, the narK gene and the narGHJI, fdnGHI, and frdABCD operons [56]. The SIDD profiles of these genes and operons are shown in Figure 6. The upstream regions of six of these seven transcriptional units are strongly destabilized, the exception being fdnGHI. In contrast, the upstream regions of internal genes in all these operons are substantially more stable.

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