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PLoS One. 2007 Nov 21;2(11):e1199.

Determining physical constraints in transcriptional initiation complexes using DNA sequence analysis.

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  • 1Department of Molecular and Cell Biology, University of California, Berkeley, United States of America.

Abstract

Eukaryotic gene expression is often under the control of cooperatively acting transcription factors whose binding is limited by structural constraints. By determining these structural constraints, we can understand the "rules" that define functional cooperativity. Conversely, by understanding the rules of binding, we can infer structural characteristics. We have developed an information theory based method for approximating the physical limitations of cooperative interactions by comparing sequence analysis to microarray expression data. When applied to the coordinated binding of the sulfur amino acid regulatory protein Met4 by Cbf1 and Met31, we were able to create a combinatorial model that can correctly identify Met4 regulated genes. Interestingly, we found that the major determinant of Met4 regulation was the sum of the strength of the Cbf1 and Met31 binding sites and that the energetic costs associated with spacing appeared to be minimal.

PMID:
18030333
PMCID:
PMC2077805
DOI:
10.1371/journal.pone.0001199
[PubMed - indexed for MEDLINE]
Free PMC Article
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