A novel link between Cell Wall Integrity pathway and Flocculation, regulated by yeast Sen1 dependent interplay between Rlm1 and Tup1

The budding yeast, Saccharomyces cerevisiae is one of the most studied organisms used for the synthesis of products, to explore the human diseases and eukaryotic gene expression mechanisms. The yeast cells with flocculation property are in high demand for industrial applications. However, the pathogenic yeast becomes drug-resistant due to flocculation/biofilm phenotype. The flocculation property of yeast depends on the expression of specific FLO genes. Genetic and epigenetic factors have been suggested to induce the expression of FLO s and flocculation, an evolutionarily conserved process. The present study was undertaken to identify a molecular link between stress caused by genetic and epigenetic factors and expression of FLO s. We utilized flocculating yeast strains to study the regulation of FLO genes and flocculation phenotype. We found rough surface morphology and constitutive activation of Slt2 in flocculating cells. The external cell wall stress factors as well as specific mutations in Sen1 and histone proteins strongly correlated with the induction of FLO genes whereas deletion of SLT2 / RLM1 , suppressed the expression and flocculation phenotype. We detected constitutive binding of Rlm1 and eviction of Tup1 from the promoters of FLO1 and FLO5 genes in flocculating cells. Thus we provide evidence for the CWI pathway dependent flocculation of yeast, regulated by Sen1 mediated interplay between Tup1 and Rlm1.