Pollard K J, Peterson C L
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester 01605, USA.
Mol Cell Biol. 1997 Nov;17(11):6212-22. doi: 10.1128/MCB.17.11.6212.
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.
酿酒酵母SWI/SNF复合物是一个2兆道尔顿的多聚体装配体，它通过拮抗染色质介导的转录抑制来促进转录增强。我们在此表明，ADA2、ADA3和GCN5中的突变，据信这些基因编码一个核组蛋白乙酰转移酶复合物的亚基，会导致与swi/snf突变体极为相似的表型。对于所测试的所有SWI/SNF依赖性基因（包括HO、SUC2、INO1和Ty元件）的完全表达，ADA2、ADA3和GCN5是必需的。此外，编码一种非组蛋白染色质成分的SIN1基因中的突变，或组蛋白H3或H4中的突变，可部分缓解由ada/gcn5或swi/snf突变所引起的转录缺陷。我们还发现ada2 swi1、ada3 swi1和gcn5 swi1双突变体无法存活，而SIN1中的突变可使这些双突变体存活。我们已部分纯化了三种色谱性质不同的GCN5依赖性乙酰转移酶活性，并表明这些酶既能使组蛋白乙酰化，也能使Sin1p乙酰化。我们提出了一个模型，其中ADA/GCN5和SWI/SNF复合物通过协同作用破坏或修饰染色质结构来促进激活因子功能。
