SNF2 5 6 AND TRANSCRIPTIONAL ACTIVATION IN YEAST

酿酒酵母的SNF2、SNF5和SNF6基因是 受不同基因调控的广泛基因的转录 机械装置。与LexA DNA结合的SNF蛋白的遗传学研究 结构域显示SNF2、SNF5和SNF6(SNF2、5、6)蛋白具有功能 在转录激活中相互依赖，可能形成一种 异构体络合物。在这里，我们建议进行研究，以阐明 SNF2、5、6蛋白参与转录激活。进一步遗传 对LexA-SNF2、5、6蛋白的激活分析将检查 SNF2、5、6相互之间以及与其他可能是 功能相关，包括SPT4、5、6、SSN6和GAL11。生化 将使用方法来确认SNF2、5、6的物理关联 复合体中的蛋白质。初步数据表明，SNF2、5、6影响 通过与多种基因的协同作用来转录多种基因 各种基因特异性转录激活剂。为了测试这一想法，我们 将研究SNF突变对LexA融合激活的影响 GAL4、BISCID、GCN4和RAP1。以确定 SNF2，5，6蛋白，我们将构建新的LexA融合蛋白，包括 部分SNF序列；异常序列特征的意义和 将检查与其他蛋白质同源的区域。最近，我们 发现了一个必需基因STH1，与SNF2的同源性在~1000以上达到60%-80% 密码子。我们建议进行研究以确定STH1蛋白是否具有 在转录激活中的作用。最后，无论是遗传还是生化 这种方法将被用来识别编码相互作用的蛋白质的基因 与SNF2，5，6物理结合。这些相互作用的蛋白质可能包括 通过以下途径促进转录激活的其他蛋白质 SNF2，5，6。最重要的是，这些研究还应确定 作为靶标的转录装置的蛋白质(S) SNF 2，5，6激活。拟议的研究将有助于我们的 对真核生物转录激活机制的认识 细胞。许多癌蛋白是转录因子，并且是异常的。 转录激活会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.