Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 histone acetyltransferase complex

The mammalian ING1 gene encodes a tumor suppressor required for the function of p53. In this study we report a novel function for YNG1, a yeast homolog of ING1. Yng1p is a stable component of the NuA3 histone acetyltransferase complex, which contains Sas3p, the yeast homolog of the mammalian MOZ proto-oncogene product, as its catalytic subunit. Yng1p is required for NuA3 function in vivo but surprisingly is not required for the integrity of the complex. Instead, we find that Yng1p mediates the interaction of Sas3p with nucleosomes and is thus required for the ability of NuA3 to modify histone tails. These data, and the observations that other ING1 homologs are found in additional yeast complexes that posttranslationally modify histones, suggest that members of the ING1 class of proteins may have broad roles in enhancing or modifying the activities of chromatin-modifying complexes, thereby regulating their activities in transcription control. Eukaryotic DNA is packaged into a nucleoprotein structure known as chromatin, consisting of DNA, histones, and nonhistone proteins. This structure is able to modulate access of the cellular machinery to DNA, thus regulating processes like transcription, replication, repair, and recombination. Numerous multiprotein complexes capable of modifying chromatin exist within a cell. The most studied of these complexes include the ATP-dependent chromatin remodeling complexes, which use the energy of ATP hydrolysis to alter the association of DNA with histones, and the histone modifying complexes, which posttranslationally modify histones. The best-characterized class of histone-modifying complexes is the histone acetyltransferases (HATs), which use acetylcoenzyme A as a substrate to acetylate lysine residues within the amino-terminal tails of histones. In the yeast Saccharomyces cerevisiae these include the GCN5-dependent SAGA,