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PMID:21552514

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Citation

Hanlon, SE, Rizzo, JM, Tatomer, DC, Lieb, JD and Buck, MJ (2011) The stress response factors Yap6, Cin5, Phd1, and Skn7 direct targeting of the conserved co-repressor Tup1-Ssn6 in S. cerevisiae. PLoS ONE 6:e19060

Abstract

Maintaining the proper expression of the transcriptome during development or in response to a changing environment requires a delicate balance between transcriptional regulators with activating and repressing functions. The budding yeast transcriptional co-repressor Tup1-Ssn6 is a model for studying similar repressor complexes in multicellular eukaryotes. Tup1-Ssn6 does not bind DNA directly, but is directed to individual promoters by one or more DNA-binding proteins, referred to as Tup1 recruiters. This functional architecture allows the Tup1-Ssn6 to modulate the expression of genes required for the response to a variety of cellular stresses. To understand the targeting or the Tup1-Ssn6 complex, we determined the genomic distribution of Tup1 and Ssn6 by ChIP-chip. We found that most loci bound by Tup1-Ssn6 could not be explained by co-occupancy with a known recruiting cofactor and that deletion of individual known Tup1 recruiters did not significantly alter the Tup1 binding profile. These observations suggest that new Tup1 recruiting proteins remain to be discovered and that Tup1 recruitment typically depends on multiple recruiting cofactors. To identify new recruiting proteins, we computationally screened for factors with binding patterns similar to the observed Tup1-Ssn6 genomic distribution. Four top candidates, Cin5, Skn7, Phd1, and Yap6, all known to be associated with stress response gene regulation, were experimentally confirmed to physically interact with Tup1 and/or Ssn6. Incorporating these new recruitment cofactors with previously characterized cofactors now explains the majority of Tup1 targeting across the genome, and expands our understanding of the mechanism by which Tup1-Ssn6 is directed to its targets.

Links

PubMed PMC3084262 Online version:10.1371/journal.pone.0019060

Keywords

Basic-Leucine Zipper Transcription Factors/deficiency; Basic-Leucine Zipper Transcription Factors/genetics; Basic-Leucine Zipper Transcription Factors/metabolism; Conserved Sequence; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Genetic Loci/genetics; Genomics; Models, Biological; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein Binding; Repressor Proteins/metabolism; Saccharomyces cerevisiae/cytology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Sequence Deletion; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:YAP4

enables

GO:0140297: DNA-binding transcription factor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:YAP6

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000353: physical interaction evidence used in manual assertion

SGD:S000000316
SGD:S000000680

P

Seeded From UniProt

complete

YEAST:YAP6

enables

GO:0001010: RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity

ECO:0000353: physical interaction evidence used in manual assertion

SGD:S000000316
SGD:S000000680

F

Seeded From UniProt

complete


See also

References

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