Abstract: The yeast GCN5 gene encodes the catalytic subunit of a nuclear histone acetyltransferase and is part of a high-molecular-weight complex involved in transcriptional regulation. In this paper we show that full activation of the HO promoter in vivo requires the Gcn5 protein and that defects in this protein can be suppressed by deletion of the RPD3 gene, which encodes a histone deacetylase. These results suggest an interplay between acetylation and deacetylation of histones in the regulation of the HO gene. We also show that mutations in either the H4 or the H3 histone gene, as well as mutations in the SIN1 gene, which encodes an HMG1-like protein, strongly suppress the defects produced by the gcn5 mutant. These results suggest a hierarchy of action in the process of chromatin remodeling.