FUNCTIONAL SIMILARITY AND PHYSICAL ASSOCIATION BETWEEN GCN5 AND ADA2 - PUTATIVE TRANSCRIPTIONAL ADAPTERS

A selection for yeast mutants resistant to GAL4-VP16-induced toxicity previously identified two genes, ADA2 and ADA3, which may function as adaptors for some transcriptional activation domains and thereby facil itate activation. Here we identify two new genes by the same selection , one of which is identical to GCN5. We show that gcn5 mutants share p roperties with ana mutants, including slow growth, temperature sensiti vity and reduced activation by the VP16 and GCN4 activation domains. D ouble mutant studies suggest that ADA2 and GCN5 function together in a complex or pathway Moreover, we demonstrate that GCN5 binds to ADA2 b oth by the two-hybrid assay in vivo and by co-immunoprecipitation in v itro. This suggests that ADA2 and GCN5 are part of a heteromeric compl ex that mediates transcriptional activation. Finally, we demonstrate t he functional importance of the bromodomain of GCN5, a sequence found in other global transcription factors such as the SWI/SNF complex and the TATA binding protein-associated factors. This domain is not requir ed for the interaction between GCN5 and ADA2 and thus may mediate a mo re general activity of transcription factors.