The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer
Silencing at the HMR and HML loci in Saccharomyces cerevisiae requires recruitment of Sir proteins to the HML and HMR silencers. The silencers are regulatory sites flanking both loci and consisting of binding sites for the Rap1, Abf1, and ORC proteins, each of which also functions at hundreds of sit...
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| Format: | Article |
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Genetics Society of America
2014
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| Online Access: | http://hdl.handle.net/1721.1/88113 |
| _version_ | 1826199116360712192 |
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| author | Teytelman, Leonid Nishimura, Erin A. Osborne Ozaydin, Bilge Eisen, Michael B. Rine, Jasper |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Teytelman, Leonid Nishimura, Erin A. Osborne Ozaydin, Bilge Eisen, Michael B. Rine, Jasper |
| author_sort | Teytelman, Leonid |
| collection | MIT |
| description | Silencing at the HMR and HML loci in Saccharomyces cerevisiae requires recruitment of Sir proteins to the HML and HMR silencers. The silencers are regulatory sites flanking both loci and consisting of binding sites for the Rap1, Abf1, and ORC proteins, each of which also functions at hundreds of sites throughout the genome in processes unrelated to silencing. Interestingly, the sequence of the binding site for Rap1 at the silencers is distinct from the genome-wide binding profile of Rap1, being a weaker match to the consensus, and indeed is bound with low affinity relative to the consensus sequence. Remarkably, this low-affinity Rap1 binding site variant was conserved among silencers of the sensu stricto Saccharomyces species, maintained as a poor match to the Rap1 genome-wide consensus sequence in all of them. We tested multiple predictions about the possible role of this binding-site variant in silencing by substituting the native Rap1 binding site at the HMR-E silencer with the genome-wide consensus sequence for Rap1. Contrary to the predictions from the current models of Rap1, we found no influence of the Rap1 binding site version on the kinetics of establishing silencing, nor on the maintenance of silencing, nor the extent of silencing. We further explored implications of these findings with regard to prevention of ectopic silencing, and deduced that the selective pressure for the unprecedented conservation of this binding site variant may not be related to silencing. |
| first_indexed | 2024-09-23T11:14:40Z |
| format | Article |
| id | mit-1721.1/88113 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:14:40Z |
| publishDate | 2014 |
| publisher | Genetics Society of America |
| record_format | dspace |
| spelling | mit-1721.1/881132022-09-27T18:07:13Z The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer Teytelman, Leonid Nishimura, Erin A. Osborne Ozaydin, Bilge Eisen, Michael B. Rine, Jasper Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Physics Teytelman, Leonid Silencing at the HMR and HML loci in Saccharomyces cerevisiae requires recruitment of Sir proteins to the HML and HMR silencers. The silencers are regulatory sites flanking both loci and consisting of binding sites for the Rap1, Abf1, and ORC proteins, each of which also functions at hundreds of sites throughout the genome in processes unrelated to silencing. Interestingly, the sequence of the binding site for Rap1 at the silencers is distinct from the genome-wide binding profile of Rap1, being a weaker match to the consensus, and indeed is bound with low affinity relative to the consensus sequence. Remarkably, this low-affinity Rap1 binding site variant was conserved among silencers of the sensu stricto Saccharomyces species, maintained as a poor match to the Rap1 genome-wide consensus sequence in all of them. We tested multiple predictions about the possible role of this binding-site variant in silencing by substituting the native Rap1 binding site at the HMR-E silencer with the genome-wide consensus sequence for Rap1. Contrary to the predictions from the current models of Rap1, we found no influence of the Rap1 binding site version on the kinetics of establishing silencing, nor on the maintenance of silencing, nor the extent of silencing. We further explored implications of these findings with regard to prevention of ectopic silencing, and deduced that the selective pressure for the unprecedented conservation of this binding site variant may not be related to silencing. National Science Foundation (U.S.) (Predoctoral Fellowship) National Institutes of Health (U.S.) (Grant GM31105) 2014-06-30T12:27:17Z 2014-06-30T12:27:17Z 2012-12 2012-08 Article http://purl.org/eprint/type/JournalArticle 2160-1836 http://hdl.handle.net/1721.1/88113 Teytelman, L., E. A. O. Nishimura, B. Ozaydin, M. B. Eisen, and J. Rine. “The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces Cerevisiae HMR-E Silencer.” G3: Genes-Genomes-Genetics 2, no. 12 (December 1, 2012): 1555–1562. en_US http://dx.doi.org/10.1534/g3.112.004077 G3: Genes-Genomes-Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Genetics Society of America Genetics Society of America |
| spellingShingle | Teytelman, Leonid Nishimura, Erin A. Osborne Ozaydin, Bilge Eisen, Michael B. Rine, Jasper The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer |
| title | The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer |
| title_full | The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer |
| title_fullStr | The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer |
| title_full_unstemmed | The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer |
| title_short | The Enigmatic Conservation of a Rap1 Binding Site in the Saccharomyces cerevisiae HMR-E Silencer |
| title_sort | enigmatic conservation of a rap1 binding site in the saccharomyces cerevisiae hmr e silencer |
| url | http://hdl.handle.net/1721.1/88113 |
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