Nucleic Acids Research Advance Access originally published online on October 5, 2007
Nucleic Acids Research 2007 35(20):6762-6777; doi:10.1093/nar/gkm631
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Nucleic Acids Research, 2007, Vol. 35, No. 20 6762-6777
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Discovery of Fur binding site clusters in Escherichia coli by information theory models
1National Cancer Institute at Frederick, Center for Cancer Research Nanobiology Program, 2Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702-1201, 3National Institute of Child Health and Human Development, Cell Biology and Metabolism Branch and 4Division of Extramural Activities, Referral and Program Analysis Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
*To whom correspondence should be addressed. Tel: +1 301 846 5581; Fax: +1 301 846 5598; Email: toms{at}ncifcrf.gov
Received June 5, 2007. Revised July 28, 2007. Accepted July 31, 2007.
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 (
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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. Present address: Karen A. Lewis, Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9040, USA. Ryan K. Shultzaberger, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA. Ming Zheng, Dupont Central Research and Development, Experimental Station E328-B31, Wilmington, DE 19880-0328, USA. Zehua Chen, Department of Biology, Boston College, MA 02467, USA.
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