title: Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo.
abstract: Gcn5p is a transcriptional coactivator required for correct expression of various genes in yeast. Several transcriptional regulators, including Gcn5p, possess intrinsic histone acetyltransferase (HAT) activity in vitro. However, whether the HAT activity of any of these proteins is required for gene activation remains unclear. Here, we demonstrate that the HAT activity of Gcn5p is critical for transcriptional activation of target genes in vivo. Core histones are hyperacetylated in cells overproducing functional Gcn5p, and promoters of Gcn5p-regulated genes 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 transcriptional 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.
authors.affiliation: Department of Biology, University of Rochester, Rochester, New York 14627, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Kuo
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: P
authors.initials: P
authors.lastname: Jambeck
authors.forename: M E
authors.initials: ME
authors.lastname: Churchill
authors.forename: C D
authors.initials: CD
authors.lastname: Allis
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D003574:Cytochrome c Group / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015003:Yeasts / Q000235:genetics / Q000254:growth & development; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C014059:CYC1 protein, S cerevisiae; D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D045304:Cytochromes c; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D011494:Protein Kinases; D001616:beta-Galactosidase; D006836:Hydro-Lyases; C021434:imidazoleglycerolphosphate dehydratase