Functional Comparison of the Tup11 and Tup12 Transcriptional Corepressors in Fission Yeast

Abstract

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 Tup12, Ssn6 is also required for efficient adaptation to KCl- 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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/.

ACKNOWLEDGMENTS

We thank Yukio Mukai (Department of Biotechnology Osaka University, Osaka, Japan) for providing strains defective in Tup proteins and Amanda Greenall and Simon Whitehall (School of Biochemistry and Genetics, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom) for providing plasmids for expression of the Tup proteins. We also thank other members of the Wright and Ekwall groups for valuable discussions and advice and particularly Karl Ekwall for comments on the manuscript. DNA microarray slides were scanned at the KI-CHIP core facility at the Karolinska Institute that is supported by the Wallenberg Foundation.

This research was funded by project grants from the Swedish Research Council and the Foundation for Strategic Research. A.P.H.W. is a senior investigator financed by the Swedish Research Council.