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Computational analyses of transcriptomic data reveal the dynamic organization of the Escherichia coli chromosome under different conditions.

Ma Q, Yin Y, Schell MA, Zhang H, Li G, Xu Y - Nucleic Acids Res. (2013)

Bottom Line: Based on this hypothesis, we have predicted seven distinct sets of such domains along the E. coli genome for seven physiological conditions, namely exponential growth, stationary growth, anaerobiosis, heat shock, oxidative stress, nitrogen limitation and SOS responses.These predicted folding domains are highly stable statistically and are generally consistent with the experimental data of DNA binding sites of the nucleoid-associated proteins that assist the folding of these domains, as well as genome-scale protein occupancy profiles, hence supporting our proposed model.Our study established for the first time a strong link between a folded E. coli chromosomal structure and the encoded biological pathways and their activation frequencies.

View Article: PubMed Central - PubMed

Affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA 30602, USA.

ABSTRACT
The circular chromosome of Escherichia coli has been suggested to fold into a collection of sequentially consecutive domains, genes in each of which tend to be co-expressed. It has also been suggested that such domains, forming a partition of the genome, are dynamic with respect to the physiological conditions. However, little is known about which DNA segments of the E. coli genome form these domains and what determines the boundaries of these domain segments. We present a computational model here to partition the circular genome into consecutive segments, theoretically suggestive of the physically folded supercoiled domains, along with a method for predicting such domains under specified conditions. Our model is based on a hypothesis that the genome of E. coli is partitioned into a set of folding domains so that the total number of unfoldings of these domains in the folded chromosome is minimized, where a domain is unfolded when a biological pathway, consisting of genes encoded in this DNA segment, is being activated transcriptionally. Based on this hypothesis, we have predicted seven distinct sets of such domains along the E. coli genome for seven physiological conditions, namely exponential growth, stationary growth, anaerobiosis, heat shock, oxidative stress, nitrogen limitation and SOS responses. These predicted folding domains are highly stable statistically and are generally consistent with the experimental data of DNA binding sites of the nucleoid-associated proteins that assist the folding of these domains, as well as genome-scale protein occupancy profiles, hence supporting our proposed model. Our study established for the first time a strong link between a folded E. coli chromosomal structure and the encoded biological pathways and their activation frequencies.

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(a) Circos plots of predicted folding domains along the genome of E. coli K12 during the stationary growth phase. The alternating black and white bands in the outermost ring represent the partition of the E. coli genome into folding domains. (b) An expanded view of the genomic region (0–1.2 M). From the inside out, the six rings are labeled with numbers: (1) Each pair of genes involved in the same EcoCyc pathway are connected using gray lines; (2) the red histogram shows the number of pathways in which the target gene is involved; (3) the orange histogram shows the number of the coexpressed gene pairs; (4) each blue bar represents the presence of a highly expressed gene; (5) each green bar represents the presence of a known NAP-binding site, which should fall in domain boundary regions; and (6) predicted folding domains represented as alternating black-and-white bands in the seventh ring. Two thick bars are used to distinguish the adjacent folding domains as the boundaries are not visible at genome scale. (c) A comparison between the numbers of coexpressed gene pairs in the flanks of the predicted domains (orange box) and a set of randomly picked intergenic regions (gray box).
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gkt261-F1: (a) Circos plots of predicted folding domains along the genome of E. coli K12 during the stationary growth phase. The alternating black and white bands in the outermost ring represent the partition of the E. coli genome into folding domains. (b) An expanded view of the genomic region (0–1.2 M). From the inside out, the six rings are labeled with numbers: (1) Each pair of genes involved in the same EcoCyc pathway are connected using gray lines; (2) the red histogram shows the number of pathways in which the target gene is involved; (3) the orange histogram shows the number of the coexpressed gene pairs; (4) each blue bar represents the presence of a highly expressed gene; (5) each green bar represents the presence of a known NAP-binding site, which should fall in domain boundary regions; and (6) predicted folding domains represented as alternating black-and-white bands in the seventh ring. Two thick bars are used to distinguish the adjacent folding domains as the boundaries are not visible at genome scale. (c) A comparison between the numbers of coexpressed gene pairs in the flanks of the predicted domains (orange box) and a set of randomly picked intergenic regions (gray box).

Mentions: We predicted the folding-domain boundaries of the E. coli genome under each of the seven classes of growth conditions shown in Table 2. One hundrerd forty-six folding domains are predicted for the exponential growth, 84 for the stationary growth, 116 for heat shock, 95 for nitrogen limitation, 94 for oxidative stress, 102 for anaerobiosis and 114 for SOS response. Figure 1a shows the predicted domains under stationary growth along the E. coli K12 genome. Figure 1b is an expanded view of the genomic region (0–1.2 M) in Figure 1a. From Figure 1b, we can see that the predicted folding domains indeed show higher levels of co-expression than gene pairs across the domain boundaries as desired, with the detailed data shown in Figure 1c. An example of the predicted domains and associated co-expression data can be found in Supplementary Example S1 and Supplementary Table S3.Figure 1.


Computational analyses of transcriptomic data reveal the dynamic organization of the Escherichia coli chromosome under different conditions.

Ma Q, Yin Y, Schell MA, Zhang H, Li G, Xu Y - Nucleic Acids Res. (2013)

(a) Circos plots of predicted folding domains along the genome of E. coli K12 during the stationary growth phase. The alternating black and white bands in the outermost ring represent the partition of the E. coli genome into folding domains. (b) An expanded view of the genomic region (0–1.2 M). From the inside out, the six rings are labeled with numbers: (1) Each pair of genes involved in the same EcoCyc pathway are connected using gray lines; (2) the red histogram shows the number of pathways in which the target gene is involved; (3) the orange histogram shows the number of the coexpressed gene pairs; (4) each blue bar represents the presence of a highly expressed gene; (5) each green bar represents the presence of a known NAP-binding site, which should fall in domain boundary regions; and (6) predicted folding domains represented as alternating black-and-white bands in the seventh ring. Two thick bars are used to distinguish the adjacent folding domains as the boundaries are not visible at genome scale. (c) A comparison between the numbers of coexpressed gene pairs in the flanks of the predicted domains (orange box) and a set of randomly picked intergenic regions (gray box).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3675479&req=5

gkt261-F1: (a) Circos plots of predicted folding domains along the genome of E. coli K12 during the stationary growth phase. The alternating black and white bands in the outermost ring represent the partition of the E. coli genome into folding domains. (b) An expanded view of the genomic region (0–1.2 M). From the inside out, the six rings are labeled with numbers: (1) Each pair of genes involved in the same EcoCyc pathway are connected using gray lines; (2) the red histogram shows the number of pathways in which the target gene is involved; (3) the orange histogram shows the number of the coexpressed gene pairs; (4) each blue bar represents the presence of a highly expressed gene; (5) each green bar represents the presence of a known NAP-binding site, which should fall in domain boundary regions; and (6) predicted folding domains represented as alternating black-and-white bands in the seventh ring. Two thick bars are used to distinguish the adjacent folding domains as the boundaries are not visible at genome scale. (c) A comparison between the numbers of coexpressed gene pairs in the flanks of the predicted domains (orange box) and a set of randomly picked intergenic regions (gray box).
Mentions: We predicted the folding-domain boundaries of the E. coli genome under each of the seven classes of growth conditions shown in Table 2. One hundrerd forty-six folding domains are predicted for the exponential growth, 84 for the stationary growth, 116 for heat shock, 95 for nitrogen limitation, 94 for oxidative stress, 102 for anaerobiosis and 114 for SOS response. Figure 1a shows the predicted domains under stationary growth along the E. coli K12 genome. Figure 1b is an expanded view of the genomic region (0–1.2 M) in Figure 1a. From Figure 1b, we can see that the predicted folding domains indeed show higher levels of co-expression than gene pairs across the domain boundaries as desired, with the detailed data shown in Figure 1c. An example of the predicted domains and associated co-expression data can be found in Supplementary Example S1 and Supplementary Table S3.Figure 1.

Bottom Line: Based on this hypothesis, we have predicted seven distinct sets of such domains along the E. coli genome for seven physiological conditions, namely exponential growth, stationary growth, anaerobiosis, heat shock, oxidative stress, nitrogen limitation and SOS responses.These predicted folding domains are highly stable statistically and are generally consistent with the experimental data of DNA binding sites of the nucleoid-associated proteins that assist the folding of these domains, as well as genome-scale protein occupancy profiles, hence supporting our proposed model.Our study established for the first time a strong link between a folded E. coli chromosomal structure and the encoded biological pathways and their activation frequencies.

View Article: PubMed Central - PubMed

Affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA 30602, USA.

ABSTRACT
The circular chromosome of Escherichia coli has been suggested to fold into a collection of sequentially consecutive domains, genes in each of which tend to be co-expressed. It has also been suggested that such domains, forming a partition of the genome, are dynamic with respect to the physiological conditions. However, little is known about which DNA segments of the E. coli genome form these domains and what determines the boundaries of these domain segments. We present a computational model here to partition the circular genome into consecutive segments, theoretically suggestive of the physically folded supercoiled domains, along with a method for predicting such domains under specified conditions. Our model is based on a hypothesis that the genome of E. coli is partitioned into a set of folding domains so that the total number of unfoldings of these domains in the folded chromosome is minimized, where a domain is unfolded when a biological pathway, consisting of genes encoded in this DNA segment, is being activated transcriptionally. Based on this hypothesis, we have predicted seven distinct sets of such domains along the E. coli genome for seven physiological conditions, namely exponential growth, stationary growth, anaerobiosis, heat shock, oxidative stress, nitrogen limitation and SOS responses. These predicted folding domains are highly stable statistically and are generally consistent with the experimental data of DNA binding sites of the nucleoid-associated proteins that assist the folding of these domains, as well as genome-scale protein occupancy profiles, hence supporting our proposed model. Our study established for the first time a strong link between a folded E. coli chromosomal structure and the encoded biological pathways and their activation frequencies.

Show MeSH
Related in: MedlinePlus