Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex
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 d...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/78006 |
| _version_ | 1811090320028336128 |
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| author | Siggers, Trevor Duyzend, Michael H. Reddy, Jessica Khan, Sidra Bulyk, Martha L. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Siggers, Trevor Duyzend, Michael H. Reddy, Jessica Khan, Sidra Bulyk, Martha L. |
| author_sort | Siggers, Trevor |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:42:24Z |
| format | Article |
| id | mit-1721.1/78006 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:42:24Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/780062022-10-01T22:06:09Z Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex Siggers, Trevor Duyzend, Michael H. Reddy, Jessica Khan, Sidra Bulyk, Martha L. 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 Duyzend, Michael H. Khan, Sidra Bulyk, Martha L. 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. National Institutes of Health (U.S.) (Grant R01 HG003985) National Institutes of Health (U.S.) (Grant U54 LM008748) National Science Foundation (U.S.) (Postdoctoral Fellowship in Biological Informatics 630639) 2013-03-27T19:35:28Z 2013-03-27T19:35:28Z 2011-12 2010-11 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/78006 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 en_US http://dx.doi.org/10.1038/msb.2011.89 Molecular Systems Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group Molecular Systems Biology/Nature Publishing Group |
| spellingShingle | Siggers, Trevor Duyzend, Michael H. Reddy, Jessica Khan, Sidra Bulyk, Martha L. Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex |
| title | Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex |
| title_full | Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex |
| title_fullStr | Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex |
| title_full_unstemmed | Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex |
| title_short | Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex |
| title_sort | non dna binding cofactors enhance dna binding specificity of a transcriptional regulatory complex |
| url | http://hdl.handle.net/1721.1/78006 |
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