Role for ADA/GCN5 products in antagonizing chromatin-mediated transcriptional repression.
The Saccharomyces cerevisiae SWI/SNF complex is a 2-MDa multimeric assembly that facilitates transcriptional enhancement by antagonizing chromatin-mediated transcriptional repression. We show here that mutations in ADA2, ADA3, and GCN5, which are believed to encode subunits of a nuclear histone acetyltransferase complex, cause phenotypes strikingly similar to that of swi/snf mutants. ADA2, ADA3, and GCN5 are required for full expression of all SWI/SNF-dependent genes tested, including HO, SUC2, INO1, and Ty elements. Furthermore, mutations in the SIN1 gene, which encodes a nonhistone chromatin component, or mutations in histone H3 or H4 partially alleviate the transcriptional defects caused by ada/gcn5 or swi/snf mutations. We also find that ada2 swi1, ada3 swi1, and gcn5 swi1 double mutants are inviable and that mutations in SIN1 allow viability of these double mutants. We have partially purified three chromatographically distinct GCN5-dependent acetyltransferase activities, and we show that these enzymes can acetylate both histones and Sin1p. We propose a model in which the ADA/GCN5 and SWI/SNF complexes facilitate activator function by acting in concert to disrupt or modify chromatin structure.
Pollard
K J
KJ
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester 01605, USA.
Peterson
C L
CL
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D051548:Histone Acetyltransferases; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D011494:Protein Kinases; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C090575:ADA2 protein, S cerevisiae; C083323:NGG1 protein, S cerevisiae; C069938:SPT2 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor