Zinc-responsive coactivator recruitment by the yeast Zap1 transcription factor

The zinc-responsive Zap1 transcription factor of Saccharomyces cerevisiae controls many genes involved in zinc homeostasis. Zap1 has two activation domains, AD1 and AD2, which are independently regulated by zinc. While AD1 can fully activate most Zap1 target genes, AD2 is active only on a subset of those genes. One hypothesis explaining this promoter specificity was that AD1 and AD2 recruit different coactivators. To address this question, we carried out a genetic screen to identify coactivator complexes that are required for Zap1-mediated activation. SWI/SNF, SAGA, and Mediator complexes were implicated as playing major roles in Zap1 activation. Consistent with this conclusion, we found that these three complexes are recruited to Zap1 target promoters in a zinc-responsive and Zap1-dependent manner. Coactivator recruitment was highly interdependent such that mutations disrupting SAGA impaired recruitment of SWI/SNF and vice versa. Optimal Mediator recruitment was dependent on both SAGA and SWI/SNF. A comparison of the coactivators recruited by AD1 and AD2 found no obvious differences suggesting that recruitment of different coactivators is not likely the mechanism of AD specificity. Rather, our results suggest that AD2 recruits coactivators less effectively than AD1 and is therefore only functional on some promoters.