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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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The Statistical Significances of the Associations of Genes in Functional Categories with the Extent of Destabilization in Their Upstream Flanks(A) GenProtEC functional categories; (B) COG classifications. In both cases, the immediate upstream 250-bp regions are used. Figures for the other two definitions of 5′ flanks are similar, and are given in Datasets S1 and S2.
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pcbi-0040017-g002: The Statistical Significances of the Associations of Genes in Functional Categories with the Extent of Destabilization in Their Upstream Flanks(A) GenProtEC functional categories; (B) COG classifications. In both cases, the immediate upstream 250-bp regions are used. Figures for the other two definitions of 5′ flanks are similar, and are given in Datasets S1 and S2.

Mentions: Figure 2A depicts the log odds scores for the distributions of genes in the SIDD0, SIDD1, SIDD2, SIDD7, and SIDD8+ groups across the 13 GenProtEC functional categories. Here, we show the results for upstream regions of 250 bp in length. (The corresponding graphs for upstream intergenic regions and for 50-bp upstream regions are similar to that shown here, and are presented in Dataset S1.) One sees that genes in five functional categories (m, r, l, ph, and o) are statistically significantly associated with SIDD0 sites at the p < 0.05 level. Category l contains only 12 genes, too few for this association to be regarded as meaningful. The categories ph (phenotype) and o (other—unknown functions) are catch-alls, each containing genes with many different types of functions. This leaves the two large and specific categories of regulators (r) and membrane proteins (m), the upstream flanks of whose genes are statistically significantly enriched in the strongest SIDD sites. Of these, the highest statistical significance occurs in the category of genes that encode regulators. There, a significance of p < 0.01 occurs in both the SIDD0 and SIDD1 groups. On the other hand, categories of RNA genes (n), and genes of external origin (h) have statistically significantly elevated numbers of genes in the SIDD8+ group, corresponding to stable 5′ upstream regions. These conclusions remain essentially unchanged for each of the three ways of defining upstream regions. (The only substantive difference is that genes encoding enzymes [e] are highly significantly represented in the SIDD8+ category when one uses intergenic regions, but not when either 50-bp or 250-bp upstream regions are used. The difference may be due to the frequency with which these genes occur in operons.)


Superhelical destabilization in regulatory regions of stress response genes.

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

The Statistical Significances of the Associations of Genes in Functional Categories with the Extent of Destabilization in Their Upstream Flanks(A) GenProtEC functional categories; (B) COG classifications. In both cases, the immediate upstream 250-bp regions are used. Figures for the other two definitions of 5′ flanks are similar, and are given in Datasets S1 and S2.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0040017-g002: The Statistical Significances of the Associations of Genes in Functional Categories with the Extent of Destabilization in Their Upstream Flanks(A) GenProtEC functional categories; (B) COG classifications. In both cases, the immediate upstream 250-bp regions are used. Figures for the other two definitions of 5′ flanks are similar, and are given in Datasets S1 and S2.
Mentions: Figure 2A depicts the log odds scores for the distributions of genes in the SIDD0, SIDD1, SIDD2, SIDD7, and SIDD8+ groups across the 13 GenProtEC functional categories. Here, we show the results for upstream regions of 250 bp in length. (The corresponding graphs for upstream intergenic regions and for 50-bp upstream regions are similar to that shown here, and are presented in Dataset S1.) One sees that genes in five functional categories (m, r, l, ph, and o) are statistically significantly associated with SIDD0 sites at the p < 0.05 level. Category l contains only 12 genes, too few for this association to be regarded as meaningful. The categories ph (phenotype) and o (other—unknown functions) are catch-alls, each containing genes with many different types of functions. This leaves the two large and specific categories of regulators (r) and membrane proteins (m), the upstream flanks of whose genes are statistically significantly enriched in the strongest SIDD sites. Of these, the highest statistical significance occurs in the category of genes that encode regulators. There, a significance of p < 0.01 occurs in both the SIDD0 and SIDD1 groups. On the other hand, categories of RNA genes (n), and genes of external origin (h) have statistically significantly elevated numbers of genes in the SIDD8+ group, corresponding to stable 5′ upstream regions. These conclusions remain essentially unchanged for each of the three ways of defining upstream regions. (The only substantive difference is that genes encoding enzymes [e] are highly significantly represented in the SIDD8+ category when one uses intergenic regions, but not when either 50-bp or 250-bp upstream regions are used. The difference may be due to the frequency with which these genes occur in operons.)

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