SNF2 5 6 AND TRANSCRIPTIONAL ACTIVATION IN YEAST

对酵母S.酿酒厂需要 广泛的基因转录，这些基因受不同的 机制等 与莱克萨DNA结合蛋白融合的SNF蛋白的遗传研究 结构域显示SNF 2、SNF 5和SNF 6（SNF 2，5，6）蛋白的功能 相互依赖的转录激活，可能形成一个 异聚复合物 在这里，我们提出的研究，以阐明的作用， SNF 2、5、6蛋白的转录激活作用。 进一步的遗传 LexA-SNF 2，5，6蛋白的激活分析将检查 SNF 2、5、6相互之间以及与其他可能 功能相关，包括SPT 4、5、6、SSN 6和GAL 11。 生化 方法将用于确认SNF的物理关联2，5，6 复合体中的蛋白质。 初步数据表明，SNF 2，5，6影响 多种基因的转录，通过与 各种基因特异性转录激活因子。 为了验证这个想法，我们 将研究snf突变对莱克萨融合激活的影响， GAL 4、Bicoid、GCN 4和RAP 1。 为了确定功能域的 SNF 2、5、6蛋白，我们将构建新的莱克萨融合蛋白， 部分SNF序列;异常序列特征的意义， 将检测与其它蛋白质同源的区域。 最近我们 鉴定了一个必需基因STH 1，其与SNF 2的同源性为60-80%，超过~1000 密码子 我们建议进行研究，以确定STH 1蛋白是否具有 在转录激活中的作用。 最后，遗传和生物化学 方法将用于识别编码蛋白质的基因， 与SNF 2，5，6物理上。 这些相互作用的蛋白质可能包括 另外的蛋白质，有助于转录激活， SNF2，5，6。 最重要的是，这些研究还应确定 转录装置的蛋白质，其是 通过SNF激活2，5，6。 建议的研究将有助于我们 理解真核生物中转录激活的机制 细胞 许多癌蛋白是转录因子，并且是异常的。 转录激活导致细胞转化和癌症。

The SNF2, SNF5, and SNF6 genes of the yeast S. cerevisiae are required for transcription of a broad range of genes that are regulated by different mechanisms. Genetic studies of SNF proteins fused to the LexA DNA-binding domain showed that the SNF2, SNF5, and SNF6 (SNF2,5,6) proteins function interdependently in transcriptional activation, probably forming a heteromeric complex. Here, we propose studies to elucidate the roles of the SNF2,5,6 proteins in transcriptional activation. Further genetic analysis of activation by the LexA-SNF2,5,6 proteins will examine the relationships of SNF2,5,6 to one another and to other proteins that may be functionally related, including SPT4,5,6 SSN6 and GAL11. Biochemical methods will be used to confirm the physical association of the SNF2,5,6 proteins in a complex. Preliminary data suggest that SNF2,5,6 affect transcription of a wide variety of genes by acting coordinately with various gene-specific transcriptional activators. To test this idea, we will examine the effects of snf mutations on activation by LexA fusions to GAL4, Bicoid, GCN4 and RAP1. To identify functional domains of the SNF2,5,6 proteins, we will construct new LexA fusion proteins containing partial SNF sequences; the significance of unusual sequence features and regions of homology to other proteins will be examined. Recently, we identified an essential gene, STH1, with 60-80% identity to SNF2 over ~1000 codons. We propose studies to determine whether the STH1 protein has a role in transcriptional activation. Finally, both genetic and biochemical approaches will be used to identify genes encoding proteins that interact physically with SNF2,5,6. These interacting proteins may include additional proteins that contribute to transcriptional activation by SNF2,5,6. Most important, these studies should also identify the protein(s) of the transcriptional apparatus that are the targets for activation by SNF2,5,6. The proposed studies will contribute to our understanding of the mechanism of transcriptional activation in eukaryotic cells. Many oncoproteins are transcription factors, and aberrant transcriptional activation results in cellular transformation and cancer.