Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex
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Siggers-2011-Non-DNA-binding cofactors enhance DNA-binding.pdf
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Author(s)
Siggers, Trevor
Duyzend, Michael H.
Reddy, Jessica
Khan, Sidra
Bulyk, Martha L.
Date Issued
December 2011
Journal
Molecular Systems Biology
Publisher
Nature Publishing Group
Citation
Siggers, Trevor et al. “Non-DNA-binding Cofactors Enhance DNA-binding Specificity of a Transcriptional Regulatory Complex.” Molecular Systems Biology 7 (2011). ©2011 Nature Publishing Group, a division of Macmillan Publishers Limited
Version
Final published version
Abstract
Recruitment of cofactors to specific DNA sites is integral for specificity in gene regulation. As a model system, we examined how targeting and transcriptional control of the sulfur metabolism genes in Saccharomyces cerevisiae is governed by recruitment of the transcriptional co-activator Met4. We developed genome-scale approaches to measure transcription factor (TF) DNA-binding affinities and cofactor recruitment to >1300 genomic binding site sequences. We report that genes responding to the TF Cbf1 and cofactor Met28 contain a novel ‘recruitment motif’ (RYAAT), adjacent to Cbf1 binding sites, which enhances the binding of a Met4–Met28–Cbf1 regulatory complex, and that abrogation of this motif significantly reduces gene induction under low-sulfur conditions. Furthermore, we show that correct recognition of this composite motif requires both non-DNA-binding cofactors Met4 and Met28. Finally, we demonstrate that the presence of an RYAAT motif next to a Cbf1 site, rather than Cbf1 binding affinity, specifies Cbf1-dependent sulfur metabolism genes. Our results highlight the need to examine TF/cofactor complexes, as novel specificity can result from cofactors that lack intrinsic DNA-binding specificity.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1038/msb.2011.89
