The Yeast AP-1 Factor Yap8 Recruits SAGA and SWI/SNF to Regulate ACR3 Expression and Arsenic Tolerance

The AP-1-like protein Yap8 is required for arsenic tolerance in the yeast Saccharomyces cerevisiae. Previous work has shown that Yap8 binds to arsenic via critical cysteine residues, which converts Yap8 into an active transcriptional regulator of the arsenic detoxification genes ACR2 and ACR3. However, how Yap8 couples arsenic sensing to gene activation is not fully understood. Here, we provide mechanistic insights into Yap8-dependent gene regulation by identifying cis-regulatory elements and regulatory factors involved. We show that full activation of ACR3 expression requires two Yap8 binding elements in the ACR3 promoter, one accessible and one occluded by a nucleosome. Arsenic stress leads to Yap8-dependent chromatin remodeling which enables Yap8 to bind also to the occluded site. We also demonstrate that Yap8 directly interacts with components of the SWI/SNF chromatin remodeling and SAGA histone acetyl transferase complexes and recruits them to the ACR3 promoter. Accordingly, the cis-regulatory elements and the SAGA and SWI/SNF complexes are all required for arsenic tolerance. Our data is consistent with a model in which arsenic binding to Yap8 results in gene activation and arsenic tolerance via Yap8-dependent recruitment of coactivators and chromatin remodeling factors to the ACR3 promoter.