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Contribution of transcription factor binding site motif variants to condition-specific gene expression patterns in budding yeast.

Rest JS, Bullaughey K, Morris GP, Li WH - PLoS ONE (2012)

Bottom Line: To accomplish this, we statistically detect motif variants with effects that differ among environments.We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1).These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, The University of Chicago, Chicago, Illinois, United States of America. Joshua.Rest@StonyBrook.edu

ABSTRACT
It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation.

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Conserved expression patterns associated with functional binding site motif variants (BSMVs).The y-axis of each plot is the mean expression (Y6.4kv6 arrays) standard error of mean shown) of the stress condition relative to the non-stress condition and the x-axis is experimental treatment, ordered by the difference between the means of genes with each BSMV (black dashes). The function of variant nucleotides at position 9 of the Reb1 binding motif is conserved in (A) Saccharomyces cerevisiae, (B) S. paradoxus, and (C) S. mikatae. In all three species, genes associated with the “G” BSMV (orange) are more highly expressed than genes associated with the “A” BSMV (green) in starvation conditions (glycerol). The function of variant nucleotides at position 10 of the Rap1 binding motif is conserved in (d) S. cerevisiae, (e) S. paradoxus, (f) S. mikatae, and (g) S. kudriavzevii. In all four species, genes associated with the “C” BSMV (blue) are more highly expressed than genes associated with the “T” BSMV (red) in starvation conditions (glycerol), and the opposite relationship is apparent during nitrogen starvation. The expression differences between the BSMVs are significantly condition-specific in panels a-f (p<0.005).
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pone-0032274-g003: Conserved expression patterns associated with functional binding site motif variants (BSMVs).The y-axis of each plot is the mean expression (Y6.4kv6 arrays) standard error of mean shown) of the stress condition relative to the non-stress condition and the x-axis is experimental treatment, ordered by the difference between the means of genes with each BSMV (black dashes). The function of variant nucleotides at position 9 of the Reb1 binding motif is conserved in (A) Saccharomyces cerevisiae, (B) S. paradoxus, and (C) S. mikatae. In all three species, genes associated with the “G” BSMV (orange) are more highly expressed than genes associated with the “A” BSMV (green) in starvation conditions (glycerol). The function of variant nucleotides at position 10 of the Rap1 binding motif is conserved in (d) S. cerevisiae, (e) S. paradoxus, (f) S. mikatae, and (g) S. kudriavzevii. In all four species, genes associated with the “C” BSMV (blue) are more highly expressed than genes associated with the “T” BSMV (red) in starvation conditions (glycerol), and the opposite relationship is apparent during nitrogen starvation. The expression differences between the BSMVs are significantly condition-specific in panels a-f (p<0.005).

Mentions: We also find that 56 out of 83 pairwise comparisons between functional BSMVs identified from an among-species comparative dataset (described below in the “conservation” discussion section) show condition specificity (Table S3). For example, the difference in regulation of genes with “G” or “A” at position 9 for the Reb1 binding sites is highest during growth in glycerol in all three Saccharomyces species examined, and therefore these experiments cluster together in Figure 3A–C.


Contribution of transcription factor binding site motif variants to condition-specific gene expression patterns in budding yeast.

Rest JS, Bullaughey K, Morris GP, Li WH - PLoS ONE (2012)

Conserved expression patterns associated with functional binding site motif variants (BSMVs).The y-axis of each plot is the mean expression (Y6.4kv6 arrays) standard error of mean shown) of the stress condition relative to the non-stress condition and the x-axis is experimental treatment, ordered by the difference between the means of genes with each BSMV (black dashes). The function of variant nucleotides at position 9 of the Reb1 binding motif is conserved in (A) Saccharomyces cerevisiae, (B) S. paradoxus, and (C) S. mikatae. In all three species, genes associated with the “G” BSMV (orange) are more highly expressed than genes associated with the “A” BSMV (green) in starvation conditions (glycerol). The function of variant nucleotides at position 10 of the Rap1 binding motif is conserved in (d) S. cerevisiae, (e) S. paradoxus, (f) S. mikatae, and (g) S. kudriavzevii. In all four species, genes associated with the “C” BSMV (blue) are more highly expressed than genes associated with the “T” BSMV (red) in starvation conditions (glycerol), and the opposite relationship is apparent during nitrogen starvation. The expression differences between the BSMVs are significantly condition-specific in panels a-f (p<0.005).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285675&req=5

pone-0032274-g003: Conserved expression patterns associated with functional binding site motif variants (BSMVs).The y-axis of each plot is the mean expression (Y6.4kv6 arrays) standard error of mean shown) of the stress condition relative to the non-stress condition and the x-axis is experimental treatment, ordered by the difference between the means of genes with each BSMV (black dashes). The function of variant nucleotides at position 9 of the Reb1 binding motif is conserved in (A) Saccharomyces cerevisiae, (B) S. paradoxus, and (C) S. mikatae. In all three species, genes associated with the “G” BSMV (orange) are more highly expressed than genes associated with the “A” BSMV (green) in starvation conditions (glycerol). The function of variant nucleotides at position 10 of the Rap1 binding motif is conserved in (d) S. cerevisiae, (e) S. paradoxus, (f) S. mikatae, and (g) S. kudriavzevii. In all four species, genes associated with the “C” BSMV (blue) are more highly expressed than genes associated with the “T” BSMV (red) in starvation conditions (glycerol), and the opposite relationship is apparent during nitrogen starvation. The expression differences between the BSMVs are significantly condition-specific in panels a-f (p<0.005).
Mentions: We also find that 56 out of 83 pairwise comparisons between functional BSMVs identified from an among-species comparative dataset (described below in the “conservation” discussion section) show condition specificity (Table S3). For example, the difference in regulation of genes with “G” or “A” at position 9 for the Reb1 binding sites is highest during growth in glycerol in all three Saccharomyces species examined, and therefore these experiments cluster together in Figure 3A–C.

Bottom Line: To accomplish this, we statistically detect motif variants with effects that differ among environments.We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1).These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, The University of Chicago, Chicago, Illinois, United States of America. Joshua.Rest@StonyBrook.edu

ABSTRACT
It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation.

Show MeSH
Related in: MedlinePlus