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Discovery of Fur binding site clusters in Escherichia coli by information theory models.

Chen Z, Lewis KA, Shultzaberger RK, Lyakhov IG, Zheng M, Doan B, Storz G, Schneider TD - Nucleic Acids Res. (2007)

Bottom Line: When the E. coli genome was scanned, we found 363 unique clusters, which includes all known Fur-repressed genes that are involved in iron metabolism.These observations suggest that Fur is either a direct repressor or an indirect activator.The Pseudomonas aeruginosa and Bacillus subtilis Fur models are highly similar to the E. coli Fur model, suggesting that the Fur-DNA recognition mechanism may be conserved for even distantly related bacteria.

View Article: PubMed Central - PubMed

Affiliation: National Cancer Institute at Frederick, Center for Cancer Research Nanobiology Program, Basic Research Program, SAIC-Frederick, Inc., Frederick, MD 21702-1201, USA.

ABSTRACT
Fur is a DNA binding protein that represses bacterial iron uptake systems. Eleven footprinted Escherichia coli Fur binding sites were used to create an initial information theory model of Fur binding, which was then refined by adding 13 experimentally confirmed sites. When the refined model was scanned across all available footprinted sequences, sequence walkers, which are visual depictions of predicted binding sites, frequently appeared in clusters that fit the footprints ( approximately 83% coverage). This indicated that the model can accurately predict Fur binding. Within the clusters, individual walkers were separated from their neighbors by exactly 3 or 6 bases, consistent with models in which Fur dimers bind on different faces of the DNA helix. When the E. coli genome was scanned, we found 363 unique clusters, which includes all known Fur-repressed genes that are involved in iron metabolism. In contrast, only a few of the known Fur-activated genes have predicted Fur binding sites at their promoters. These observations suggest that Fur is either a direct repressor or an indirect activator. The Pseudomonas aeruginosa and Bacillus subtilis Fur models are highly similar to the E. coli Fur model, suggesting that the Fur-DNA recognition mechanism may be conserved for even distantly related bacteria.

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Related in: MedlinePlus

Different alignments of footprinted E. coli Fur binding sites. Sequence alignments were done using the program malign with different window sizes [from (−15, +15) to (−5, +5)] (17) on 11 footprinted E. coli Fur binding sequences and their complements (see Supplementary Figure S1 for sequences). Three classes of alignments, M12 (A), M9 (B) and M6 (C) were obtained by using window sizes of (−12, +12), (−9, +9) and (−6, +6), respectively. In these logos, the height of each letter is proportional to the frequency of that base at each position, and the height of the letter stack is the conservation in bits (18). The dashed sine wave on each logo represents the 10.6 base helical twist of B-form DNA (31,81). The double dashed arrows on the top of each logo mark the inverted repeats in each model. Note that the M12 logo corresponds to two overlapping M9 sites, as indicated by the two red double dashed arrows below the M12 logo. A similar relationship occurs between the M9 and M6 logos.
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Figure 1: Different alignments of footprinted E. coli Fur binding sites. Sequence alignments were done using the program malign with different window sizes [from (−15, +15) to (−5, +5)] (17) on 11 footprinted E. coli Fur binding sequences and their complements (see Supplementary Figure S1 for sequences). Three classes of alignments, M12 (A), M9 (B) and M6 (C) were obtained by using window sizes of (−12, +12), (−9, +9) and (−6, +6), respectively. In these logos, the height of each letter is proportional to the frequency of that base at each position, and the height of the letter stack is the conservation in bits (18). The dashed sine wave on each logo represents the 10.6 base helical twist of B-form DNA (31,81). The double dashed arrows on the top of each logo mark the inverted repeats in each model. Note that the M12 logo corresponds to two overlapping M9 sites, as indicated by the two red double dashed arrows below the M12 logo. A similar relationship occurs between the M9 and M6 logos.

Mentions: Eleven footprinted Fur binding sites (see Table 3 and Supplementary Figure S1) (8,32–39) from E. coli K-12 (53) were used to create an initial information theory model. Because Fur binds as a dimer (9,54), the model included both the footprinted Fur sequences and their complements. The sequences were aligned using the program malign, which maximizes the information content within a region of the alignment (a ‘window’) by shuffling the sequences back and forth (17). Multiple alignment with a window size of (−12, +12) gave a sequence logo that shows base conservation in the range of (−12, +12) (Figure 1A). For convenience we named this logo M12.Figure 1.


Discovery of Fur binding site clusters in Escherichia coli by information theory models.

Chen Z, Lewis KA, Shultzaberger RK, Lyakhov IG, Zheng M, Doan B, Storz G, Schneider TD - Nucleic Acids Res. (2007)

Different alignments of footprinted E. coli Fur binding sites. Sequence alignments were done using the program malign with different window sizes [from (−15, +15) to (−5, +5)] (17) on 11 footprinted E. coli Fur binding sequences and their complements (see Supplementary Figure S1 for sequences). Three classes of alignments, M12 (A), M9 (B) and M6 (C) were obtained by using window sizes of (−12, +12), (−9, +9) and (−6, +6), respectively. In these logos, the height of each letter is proportional to the frequency of that base at each position, and the height of the letter stack is the conservation in bits (18). The dashed sine wave on each logo represents the 10.6 base helical twist of B-form DNA (31,81). The double dashed arrows on the top of each logo mark the inverted repeats in each model. Note that the M12 logo corresponds to two overlapping M9 sites, as indicated by the two red double dashed arrows below the M12 logo. A similar relationship occurs between the M9 and M6 logos.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2189734&req=5

Figure 1: Different alignments of footprinted E. coli Fur binding sites. Sequence alignments were done using the program malign with different window sizes [from (−15, +15) to (−5, +5)] (17) on 11 footprinted E. coli Fur binding sequences and their complements (see Supplementary Figure S1 for sequences). Three classes of alignments, M12 (A), M9 (B) and M6 (C) were obtained by using window sizes of (−12, +12), (−9, +9) and (−6, +6), respectively. In these logos, the height of each letter is proportional to the frequency of that base at each position, and the height of the letter stack is the conservation in bits (18). The dashed sine wave on each logo represents the 10.6 base helical twist of B-form DNA (31,81). The double dashed arrows on the top of each logo mark the inverted repeats in each model. Note that the M12 logo corresponds to two overlapping M9 sites, as indicated by the two red double dashed arrows below the M12 logo. A similar relationship occurs between the M9 and M6 logos.
Mentions: Eleven footprinted Fur binding sites (see Table 3 and Supplementary Figure S1) (8,32–39) from E. coli K-12 (53) were used to create an initial information theory model. Because Fur binds as a dimer (9,54), the model included both the footprinted Fur sequences and their complements. The sequences were aligned using the program malign, which maximizes the information content within a region of the alignment (a ‘window’) by shuffling the sequences back and forth (17). Multiple alignment with a window size of (−12, +12) gave a sequence logo that shows base conservation in the range of (−12, +12) (Figure 1A). For convenience we named this logo M12.Figure 1.

Bottom Line: When the E. coli genome was scanned, we found 363 unique clusters, which includes all known Fur-repressed genes that are involved in iron metabolism.These observations suggest that Fur is either a direct repressor or an indirect activator.The Pseudomonas aeruginosa and Bacillus subtilis Fur models are highly similar to the E. coli Fur model, suggesting that the Fur-DNA recognition mechanism may be conserved for even distantly related bacteria.

View Article: PubMed Central - PubMed

Affiliation: National Cancer Institute at Frederick, Center for Cancer Research Nanobiology Program, Basic Research Program, SAIC-Frederick, Inc., Frederick, MD 21702-1201, USA.

ABSTRACT
Fur is a DNA binding protein that represses bacterial iron uptake systems. Eleven footprinted Escherichia coli Fur binding sites were used to create an initial information theory model of Fur binding, which was then refined by adding 13 experimentally confirmed sites. When the refined model was scanned across all available footprinted sequences, sequence walkers, which are visual depictions of predicted binding sites, frequently appeared in clusters that fit the footprints ( approximately 83% coverage). This indicated that the model can accurately predict Fur binding. Within the clusters, individual walkers were separated from their neighbors by exactly 3 or 6 bases, consistent with models in which Fur dimers bind on different faces of the DNA helix. When the E. coli genome was scanned, we found 363 unique clusters, which includes all known Fur-repressed genes that are involved in iron metabolism. In contrast, only a few of the known Fur-activated genes have predicted Fur binding sites at their promoters. These observations suggest that Fur is either a direct repressor or an indirect activator. The Pseudomonas aeruginosa and Bacillus subtilis Fur models are highly similar to the E. coli Fur model, suggesting that the Fur-DNA recognition mechanism may be conserved for even distantly related bacteria.

Show MeSH
Related in: MedlinePlus