Individual Subunits of the Ssn6-Tup11/12 Corepressor Are Selectively Required for Repression of Different Target Genes

Abstract

The Saccharomyces cerevisiae Ssn6 and Tup1 proteins form a corepressor complex that is recruited to target genes by DNA-bound repressor proteins. Repression occurs via several mechanisms, including interaction with hypoacetylated N termini of histones, recruitment of histone deacetylases (HDACs), and interactions with the RNA polymerase II holoenzyme. The distantly related fission yeast, Schizosaccharomyces pombe, has two partially redundant Tup1-like proteins that are dispensable during normal growth. In contrast, we show that Ssn6 is an essential protein in S. pombe, suggesting a function that is independent of Tup11 and Tup12. Consistently, the group of genes that requires Ssn6 for their regulation overlaps but is distinct from the group of genes that depend on Tup11 or Tup12. Global chip-on-chip analysis shows that Ssn6 is almost invariably found in the same genomic locations as Tup11 and/or Tup12. All three corepressor subunits are generally bound to genes that are selectively regulated by Ssn6 or Tup11/12, and thus, the subunit specificity is probably manifested in the context of a corepressor complex containing all three subunits. The corepressor binds to both the intergenic and coding regions of genes, but differential localization of the corepressor 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. Clr6 is also important for the repression of corepressor target genes. Interestingly, a subset of corepressor target genes, including direct target genes affected by Ssn6 overexpression, is associated with the function of class II (Clr3) and III (Hst4 and Sir2) HDACs.

Crystal Structure of the N-terminal Domain of the Yeast General Corepressor Tup1p and Its Functional Implications

“…Tup1p may therefore be responsible for repressor activity, with Cyc8p possibly serving as a bridge between Tup1p and other proteins. S. cerevisiae CYC8, not TUP1, is required for normal growth (30), and the S. pombe ssn6 ϩ gene has also been shown to be essential for growth (31).…”

The Schizosaccharomyces pombe inv1 + Regulatory Region Is Unusually Large and Contains Redundant cis -Acting Elements That Function in a SAGA- and Swi/Snf-Dependent Fashion

“…Previous studies had demonstrated that inv1 ϩ is transcriptionally repressed in high glucose and induced in low glucose (19,35) and that glucose repression depends upon Scr1 and Ssn6/Tup (9,35). Our results show that inv1 ϩ is under the control of a complex set of regulatory elements, spread over approximately 2 kb, a size considerably larger than that normally observed for yeast genes.…”

“…Previous studies have shown that inv1 ϩ transcription is repressed in high glucose and induced in low glucose, yet its regulation is distinct from that of another glucose-regulated gene, fbp1 ϩ (19,35). Additional work has shown that repression of inv1 ϩ in high glucose requires the factors Scr1 (35) and Ssn6/Tup (9). Furthermore, inv1 ϩ is regulated by histone acetylation, as a histone deacetylase, Clr6, is required for the full repression of inv1 ϩ , acetylation of H3K14, H4K12, H4K16, and H4K5 in the intergenic region of inv1 ϩ is elevated in a clr6-1 mutant, and inv1 ϩ mRNA levels are decreased in the absence of the histone acetyltransferase Elp1 (28,38).…”

Regulation of carotenogenesis in the red yeast Xanthophyllomyces dendrorhous: the role of the transcriptional co-repressor complex Cyc8–Tup1 involved in catabolic repression

“…This is not surprising because it has been previously reported in S. cerevisiae and in other microorganisms that the repression activity of each component of the co-repressor complex may vary depending on the target gene. For example, unlike the TUP1 gene, the CYC8 gene is essential for viability in Schizosaccharomyces pombe [44–46]. In addition based on reports that Cyc8 forms a bridge between the DNA-binding regulator and Tup1 [44, 47], Tup1 may not be recruited to the target promoters in the absence of Cyc8.…”