Thermodynamic favorability of transcription factor (TF) binding to DNA is a significant factor in the control of gene expression. Theoretical and in vitro measures link the relative equilibrium energy of a particular DNA binding protein to the sequence variation among binding sites in a genome. Extending this principle, we investigate whether biological variation in expression levels of active proteins leads to regulation of different sets of genes, based on inferred affinities of sites upstream of those genes. The TF-concentration-dependent variation in the repertoire of genes regulated by a particular TF is expected to follow patterns of chemical partitioning over DNA sites having differing affinity, and we develop a new modeling approach to test this hypothesis. Based on computational TF binding site discovery and genome-wide expression data available in Saccharomyces cerevisiae, we explore motif content for sets of genes and conditions having varying concentrations of different transcription factors which turn those genes on or off. We find cases of significant correlation between the level of intragenomic motif sequence variation and modeled TF protein levels that actuates regulation of corresponding sets of genes, and discuss the observed TF motif variants for several yeast transcription factors, as well as the potential biological functions of genes that are regulated by differential response to these high and low concentrations of particular TFs. These findings suggest that motif sequences of transcription factor binding sites may often be linked with the expression state of corresponding DNA-binding proteins.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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