Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex
Author(s)Siggers, Trevor; Duyzend, Michael H.; Reddy, Jessica; Khan, Sidra; Bulyk, Martha L.
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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.
DepartmentHarvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering
Molecular Systems Biology
Nature Publishing Group
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
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