Specificity and Robustness in Transcription Control Networks

Recognition by transcription factors of the regulatory DNA elements upstream of genes is the fundamental step in controlling gene expression. How does the necessity to provide stability with respect to mutation constrain the organization of transcription control networks? We examine the mutation loa...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-02, Vol.99 (4), p.2072-2077
Main Authors: Sengupta, Anirvan M., Djordjevic, Marko, Shraiman, Boris I.
Format: Article
Language:English
Subjects:
Algorithms
Bacteria
Binding energy
Binding Sites
Biological Evolution
Biological Sciences
Deoxyribonucleic acid
DNA
DNA - genetics
DNA - metabolism
DNA-Binding Proteins - metabolism
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Evolution
Genes
Genetic mutation
Genetics
Genomics
Models, Statistical
Mutation
Pleiotropy
Regulon
Response Elements
Transcription Factors
Transcription, Genetic
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Summary:Recognition by transcription factors of the regulatory DNA elements upstream of genes is the fundamental step in controlling gene expression. How does the necessity to provide stability with respect to mutation constrain the organization of transcription control networks? We examine the mutation load of a transcription factor interacting with a set of n regulatory response elements as a function of the factor/DNA binding specificity and conclude on theoretical grounds that the optimal specificity decreases with n. The predicted correlation between variability of binding sites (for a given transcription factor) and their number is supported by the genomic data for Escherichia coli. The analysis of E. coli genomic data was carried out using an algorithm suggested by the biophysical model of transcription factor/DNA binding. Complete results of the search for candidate transcription factor binding sites are available at http://www.physics.rockefeller.edu/~boris/public/search_ecoli.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.022388499