The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae

We have identified two Gcn5-dependent histone acetyltransferase (HAT) compl exes from Saccharomyces cerevisiae, the 0.8-MDa ADA complex and the 1.8-MDa SAGA complex. The SAGA (Spt-Ada-Gcn5-acetyltransferase) complex contains s everal subunits which also function as part of other protein complexes, inc luding a subset of TATA box binding protein-associated factors (TAFIIs) and Tra1. These observations raise the question of whether the 0.8-MDa ADA com plex is a subcomplex of SAGA or whether it is a distinct HAT complex that a lso shares subunits with SAGA. To address this issue, we sought to determin e if the ADA complex contained subunits that are not present in the SAGA co mplex. In this study, we report the purification of the ADA complex over 10 chromatographic steps. By a combination of mass spectrometry analysis and immunoblotting, we demonstrate that the adapter proteins Ada2, Ada3, and Gc n5 are indeed integral components of ADA. Furthermore, we identify the prod uct of the S. cerevisiae gene YOR023C as a novel subunit of the ADA complex and name it Ahc1 for ADA HAT complex component I. Biochemical functions of YOR023C have not been reported. However, AHC1 in high copy numbers suppres ses the cold sensitivity caused by particular mutations in HTA1 (I. Pinto a nd F. Winston, personal communication), which encodes histone H2A (J. N. Hi rschhorn et al., Mol. Cell. Biol. 15:1999-2009, 1995). Deletion of AHC1 dis rupted the integrity of the ADA complex but did not affect SAGA or give ris e to classic Ada(-) phenotypes. These results indicate that Gcn5, Ada2, and Ada3 function as part of a unique HAT complex (ADA) and represent shared s ubunits between this complex and SAGA.