HISTONE ACETYLTRANSFERASE ACTIVITY OF YEAST GCN5P IS REQUIRED FOR THEACTIVATION OF TARGET GENES IN-VIVO

Gcn5p is a transcriptional coactivator required for correct expression of various genes in yeast. Several transcriptional regulators, includ ing Gcn5p, possess intrinsic histone acetyltransferase (HAT) activity in vitro. However, whether the HAT activity of any of these proteins i s required for gene activation remains unclear. Here, we demonstrate t hat the HAT activity of Gcn5p is critical for transcriptional activati on of target genes in vivo. Core histones are hyperacetylated in cells overproducing functional Gcn5p, and promoters of Gcn5p-regulated gene s are associated with hyperacetylated histones upon activation by low- copy Gcn5p. Point mutations within the Gcn5p catalytic domain abolish both promoter-directed histone acetylation and Gcn5p-mediated transcri ptional activation. These data provide the first in vivo evidence that promoter-specific histone acetylation, catalyzed by functional Gcn5p, plays a critical role in gene activation.