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Evolutionary comparisons suggest many novel cAMP response protein binding sites in Escherichia coli

Brown, C. T. and Callan, Jr., C. G. (2004) Evolutionary comparisons suggest many novel cAMP response protein binding sites in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America, 101 (8). pp. 2404-2409. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:BROpnas04

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Abstract

The cAMP response protein (CRP) is a transcription factor known to regulate many genes in Escherichia coli. Computational studies of transcription factor binding to DNA are usually based on a simple matrix model of sequence-dependent binding energy. For CRP, this model predicts many binding sites that are not known to be functional. If they are indeed spurious, the underlying binding model is called into question. We use a species comparison method to assess the functionality of a population of such predicted CRP sites in E. coli. We compare them with orthologous sites in Salmonella typhimurium identified independently by CLUSTALW alignment, and find a dependence of mutation probability on position in the site. This dependence increases with predicted site binding energy. The positions where mutation is most strongly suppressed are those where mutation would have the biggest effect on predicted binding energy. This finding suggests that many of the novel sites are functional, that the matrix model correctly estimates their binding strength, and that calculated CRP binding strength is the quantity that is conserved between species. The analysis also identifies many new E. coli binding sites and genes likely to be functional for CRP.


Item Type:Article
Additional Information:Copyright © 2004 by the National Academy of Sciences. Contributed by C. G. Callan, Jr., December 23, 2003. We thank Erich M. Schwarz, Paola Oliveri, and Saeed Tavazoie for useful discussions, Nikolaus Rajewsky and Leonid Kruglyak for careful reading of the manuscript and helpful suggestions, and Eric H. Davidson, R. Andrew Cameron, and the Beckman Institute Center for Computational Regulatory Genomics at the California Institute of Technology for access to their computational resources (supported by National Institutes of Health Grant RR15044). C.T.B. was supported by National Institutes of Health Grant GM61005 to E. H. Davidson.
Subject Keywords:regulatory proteins, comparative genomics, drosophila embryo, selection, recognition, discovery, regulons
Record Number:CaltechAUTHORS:BROpnas04
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:BROpnas04
Alternative URL:http://dx.doi.org/10.1073/pnas.0308628100
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:894
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Nov 2005
Last Modified:14 Nov 2014 19:18

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