1. Department of Biological Chemistry, UCLA School of Medicine and the Molecular Biology Institute, Boyer Hall, University of California, Los Angeles, California 90095, USA

Correspondence to: Michael Grunstein Correspondence and requests for materials should be addressed to M.G. (e-mail: Email: mg@mbi.ucla.edu).

Histone acetyltransferases and deacetylases can be targeted to promoters to activate or repress genes. For example, the histone acetyltransferase GCN5 is part of a yeast multiprotein complex that is recruited by the DNA-binding activator protein GCN4 (refs 1, 2,3). The histone deacetylase RPD3 complex is recruited to DNA by the repressor UME6 (refs 4, 5); similar mechanisms exist in other eukaryotes⁶. However, deletion of RPD3 also increases expression of the PHO5 gene⁷ that is repressed by nucleosomes^{8, 9}, and regulated by GCN5 (ref. 10) but not by UME6. We have determined whether acetylation and deacetylation are promoter specific at PHO5, by using antibodies against acetylated lysine residues and chromatin immunoprecipitation to examine the acetylation state of a 4.25-kilobase region surrounding the PHO5 gene. Here we show that this region is acetylated extensively by ESA1 and GCN5 and deacetylated by HDA1 and RPD3, and that widespread histone modification affects three separate chromosomal regions examined, which total 22 kb. Our data indicate that targeted modification occurs in a background of global acetylation and deacetylation that not only reduces basal transcription, but also allows a rapid return to the initial state of acetylation when targeting is removed.