Yousef Ahmed F, Brandl Christopher J, Mymryk Joe S
Department of Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada.
BMC Mol Biol. 2009 Apr 17;10:32. doi: 10.1186/1471-2199-10-32.
The human adenovirus type 5 early region 1A (E1A) gene encodes proteins that are potent regulators of transcription. E1A does not bind DNA directly, but is recruited to target promoters by the interaction with sequence specific DNA binding proteins. In mammalian systems, E1A has been shown to contain two regions that can independently induce transcription when fused to a heterologous DNA binding domain. When expressed in Saccharomyces cerevisiae, each of these regions of E1A also acts as a strong transcriptional activator. This allows yeast to be used as a model system to study mechanisms by which E1A stimulates transcription.
Using 81 mutant yeast strains, we have evaluated the effect of deleting components of the ADA, COMPASS, CSR, INO80, ISW1, NuA3, NuA4, Mediator, PAF, RSC, SAGA, SAS, SLIK, SWI/SNF and SWR1 transcriptional regulatory complexes on E1A dependent transcription. In addition, we examined the role of histone H2B ubiquitylation by Rad6/Bre1 on transcriptional activation.
Our analysis indicates that the two activation domains of E1A function via distinct mechanisms, identify new factors regulating E1A dependent transcription and suggest that yeast can serve as a valid model system for at least some aspects of E1A function.
人5型腺病毒早期区域1A（E1A）基因编码的蛋白质是强效转录调节因子。E1A不直接结合DNA，而是通过与序列特异性DNA结合蛋白相互作用被招募到目标启动子上。在哺乳动物系统中，E1A已被证明含有两个区域，当与异源DNA结合结构域融合时，这两个区域可独立诱导转录。当在酿酒酵母中表达时，E1A的这些区域中的每一个也都作为强大的转录激活因子起作用。这使得酵母能够用作研究E1A刺激转录机制的模型系统。
我们使用81个突变酵母菌株，评估了缺失ADA、COMPASS、CSR、INO80、ISW1、NuA3、NuA4、中介体、PAF、RSC、SAGA、SAS、SLIK、SWI/SNF和SWR1转录调节复合物的组分对E1A依赖性转录的影响。此外，我们研究了Rad6/Bre1介导的组蛋白H2B泛素化在转录激活中的作用。
我们的分析表明，E1A的两个激活结构域通过不同机制发挥作用，鉴定了调节E1A依赖性转录的新因子，并表明酵母可作为至少某些方面E1A功能的有效模型系统。
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