| Title: | Genetic analysis argues for a coactivator function for the Saccharomyces cerevisiae Tup1 corepressor |
| Author(s): | Parnell EJ; Parnell TJ; Stillman DJ; |
| Address: | "Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA. Bioinformatics Shared Resource, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA" |
| ISSN/ISBN: | 1943-2631 (Electronic) 0016-6731 (Print) 0016-6731 (Linking) |
| Abstract: | "The Tup1-Cyc8 corepressor complex of Saccharomyces cerevisiae is recruited to promoters by DNA-binding proteins to repress transcription of genes, including the a-specific mating-type genes. We report here a tup1(S649F) mutant that displays mating irregularities and an alpha-predominant growth defect. RNA-Seq and ChIP-Seq were used to analyze gene expression and Tup1 occupancy changes in mutant vs wild type in both a and alpha cells. Increased Tup1(S649F) occupancy tended to occur upstream of upregulated genes, whereas locations with decreased occupancy usually did not show changes in gene expression, suggesting this mutant not only loses corepressor function but also behaves as a coactivator. Based upon studies demonstrating a dual role of Tup1 in both repression and activation, we postulate that the coactivator function of Tup1(S649F) results from diminished interaction with repressor proteins, including alpha2. We also found that large changes in mating-type-specific gene expression between a and alpha or between mutant and wild type were not easily explained by the range of Tup1 occupancy levels within their promoters, as predicted by the classic model of a-specific gene repression by Tup1. Most surprisingly, we observed Tup1 occupancy upstream of the a-specific gene MFA2 and the alpha-specific gene MF(ALPHA)1 in cells in which each gene was expressed rather than repressed. These results, combined with the identification of additional mating-related genes upregulated in the tup1(S649F) alpha strain, illustrate that the role of Tup1 in distinguishing mating types in yeast appears to be both more comprehensive and more nuanced than previously appreciated" |
| Keywords: | "*Gene Expression Regulation, Fungal Lipoproteins/genetics/metabolism Nuclear Proteins/genetics/*metabolism Pheromones/genetics/metabolism Promoter Regions, Genetic Repressor Proteins/genetics/*metabolism Saccharomyces cerevisiae Saccharomyces cerevisiae P;" |
| Notes: | "MedlineParnell, Emily J Parnell, Timothy J Stillman, David J eng R01 GM121079/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2021/12/02 Genetics. 2021 Oct 2; 219(2):iyab120. doi: 10.1093/genetics/iyab120" |
