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Functional comparison of the Tup11 and Tup12 transcriptional corepressors in fission yeast
Södertörn University, School of Life Sciences. Karolinska Institutet.
Södertörn University, School of Life Sciences. Karolinska Institutet.ORCID iD: 0000-0003-1029-9969
2005 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 25, no 2, 716-727 p.Article in journal (Refereed) Published
Abstract [en]

Gene duplication is considered an important evolutionary mechanism. Unlike many characterized species, the fission yeast Schizosaccharomyces pombe contains two paralogous genes, tup11(+) and tup12(+), that encode transcriptional corepressors similar to the well-characterized budding yeast Tup1 protein. Previous reports have suggested that Tup11 and Tup12 proteins play redundant roles. Consistently, we show that the two Tup proteins can interact together when expressed at normal levels and that each can independently interact with the Ssn6 protein, as seen for Tup1 in budding yeast. However, tup11(-) and tup12(-) mutants have different phenotypes on media containing KCl and CaCl2. Consistent with the functional difference between tup11(-) and tup12- mutants, we identified a number of genes in genome-wide gene expression experiments that are differentially affected by mutations in the tup11(+) and tup12(+) genes. Many of these genes are differentially derepressed in tup11(-) mutants and are over-represented in genes that have previously been shown to respond to a range of different stress conditions. Genes specifically derepressed in tup12(-) mutants require the Ssn6 protein for their repression. As for Tupl.2, Ssn6 is also required for efficient adaptation to KCI- and CaCl2-mediated stress. We conclude that Tup11 and Tup12 are at least partly functionally diverged and suggest that the Tup12 and Ssn6 proteins have adopted a specific role in regulation of the stress response.

Place, publisher, year, edition, pages
2005. Vol. 25, no 2, 716-727 p.
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:sh:diva-14401DOI: 10.1128/MCB.25.2.716-727.2005ISI: 000226287800018PubMedID: 15632072Scopus ID: 2-s2.0-11844294040OAI: oai:DiVA.org:sh-14401DiVA: diva2:468842
Available from: 2011-12-21 Created: 2011-12-21 Last updated: 2017-07-19Bibliographically approved
In thesis
1. Genome wide analysis of the Ssn6-Tup11/Tup12 co-repressor complex in the fission yeast Schizosaccharomyces pombe
Open this publication in new window or tab >>Genome wide analysis of the Ssn6-Tup11/Tup12 co-repressor complex in the fission yeast Schizosaccharomyces pombe
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this study, we have investigated the fission yeast Ssn6-Tup11 /Tup 12 transcriptional corepressor which is involved in regulation of many genes important for a wide variety of processes. In contrast to the well characterised budding yeast Tup1 protein there are two paralogous proteins present in fission yeast, namely Tup11 and Tup12. We have shown that the two proteins can interact with each other and are expressed at similar levels, which is in line with a reported redundant function. Sequence analysis shows that the intermediate proposed histone interacting domain is highly variable between Tup11 and Tup12 indicating a diversification. Interestingly, we show that tup11 and tup12 mutants have different phenotypes on media containing KC1 and CaC12. Consistent with this functional difference, we identify a number of target genes by genome wide expression profiling that are differentially affected by tup11 - and tup12. Many of these genes are Tup12 dependent and correlate with genes that have previously been shown to respond to a range of different environmental stress conditions. The observed different physiological roles of Tup11 and Tup12 can not be explained by differential recruitment of Ssn6 which can interact independently with both Tup11 and Tup12. Most interestingly we show that the Ssn6 protein is essential in fission yeast and therefore must have a distinct role separated from Tup11 and Tup12. Surprisingly, a conditional ssn6HA-ts mutant displays the same growth phenotype as tup12, indicating a role in Tup12 dependent stress response. Consistent with the diverse phenotypes of the individual co-repressor proteins, we identify a group of genes that requires Ssn6 for their regulation which is overlapping but distinct from the group of genes that depend on Tup11 or Tup12. Genome wide chromatin immunoprecipitation shows that Ssn6 is almost invariably found in the same genomic locations as Tup11 and/or Tup12. All three co-repressor subunits are generally bound to genes that are selectively regulated by Ssn6 or Tup11/12, and thus, likely in the context of a co-repressor complex containing all three subunits. The co-repressor binds to both the intergenic and coding regions of genes, but differential localization of the co-repressor within genes does not appear to account for the selective dependence of target genes on the Ssn6 or Tup11/12 subunits. Ssn6, Tup11, and Tup12 are preferentially found at genomic locations at which histones are deacetylated, primarily by the Clr6 class I HDAC. A subset of co-repressor target genes, including direct target genes affected by Ssn6 overexpression, is in addition associated with the function of class II (Clr3) and III (Hst4 and Sir2) HDACs. Interestingly, many specific Hst4 repressed ORF targets involved in amino acid biosynthesis are also direct targets for the Ssn6-Tup11/12 co-repressor, suggesting an association with the class ill sirtuins which has not been reported previously.

Place, publisher, year, edition, pages
Stockholm: Karolinska instiutet, 2007. 58 p.
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-31991 (URN)978-91-7357-120-3 (ISBN)
Public defence
2007-03-08, MB416, Alfred Nobels allé 7, Huddinge, 10:00 (English)
Opponent
Supervisors
Available from: 2017-02-08 Created: 2017-02-08 Last updated: 2017-02-08Bibliographically approved

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Fagerström-Billai, FredrikWright, Anthony P H

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