Systematic analysis of tup1 and cyc8 mutants reveals distinct roles for TUP1 and CYC8 and offers new insight into the regulation of gene transcription by the yeast Tup1-Cyc8 complex

The Tup1-Cyc8 complex in Saccharomyces cerevisiae was one of the first global co-repressors of gene transcription discovered. However, despite years of study, a full understanding of the contribution of Tup1p and Cyc8p to complex function is lacking. We examined TUP1 and CYC8 single and double delet...

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Published in:PLoS genetics 2023-08, Vol.19 (8), p.e1010876-e1010876
Main Authors: Lee, Brenda, Church, Michael, Hokamp, Karsten, Alhussain, Mohamed M, Bamagoos, Atif A, Fleming, Alastair B
Format: Article
Language:English
Subjects:
Analysis
Biology and life sciences
Brewer's yeast
Cells
Deletion mutant
Ethylenediaminetetraacetic acid
Gene regulation
Gene silencing
Genes
Genetic aspects
Genetic research
Genetic transcription
Genotype & phenotype
Histones
Morphology
Mutants
Phenotype
Physical Sciences
Proteins
Repressors
Research and Analysis Methods
Transcription
Transcription factors
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Summary:The Tup1-Cyc8 complex in Saccharomyces cerevisiae was one of the first global co-repressors of gene transcription discovered. However, despite years of study, a full understanding of the contribution of Tup1p and Cyc8p to complex function is lacking. We examined TUP1 and CYC8 single and double deletion mutants and show that CYC8 represses more genes than TUP1, and that there are genes subject to (i) unique repression by TUP1 or CYC8, (ii) redundant repression by TUP1 and CYC8, and (iii) there are genes at which de-repression in a cyc8 mutant is dependent upon TUP1, and vice-versa. We also reveal that Tup1p and Cyc8p can make distinct contributions to commonly repressed genes most likely via specific interactions with different histone deacetylases. Furthermore, we show that Tup1p and Cyc8p can be found independently of each other to negatively regulate gene transcription and can persist at active genes to negatively regulate on-going transcription. Together, these data suggest that Tup1p and Cyc8p can associate with active and inactive genes to mediate distinct negative and positive regulatory roles when functioning within, and possibly out with the complex.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1010876