Wright A P, McEwan I J, Dahlman-Wright K, Gustafsson J A
Department of Medical Nutrition, Karolinska Institute, NOVUM Huddinge University Hospital, Sweden.
Mol Endocrinol. 1991 Oct;5(10):1366-72. doi: 10.1210/mend-5-10-1366.
A number of alternative mechanisms by which the DNA-bound glucocorticoid receptor transactivates gene expression have been suggested. The fact that the glucocorticoid and other steroid hormone receptors function in yeast suggests that at least one of these mechanisms has been conserved throughout evolution. Here we show that overexpression of one of the glucocorticoid receptor transactivation domains (tau 1) in yeast causes a reduction in expression of a yeast reporter gene, followed by a severe reduction in the growth rate of the yeast cells. This is analogous to the phenomenon of squelching, first described for the GAL4 protein, and suggests that the tau 1 domain of the glucocorticoid receptor functions by contacting limiting transcription factors needed for efficient gene activity. A similar level of squelching was seen after removal of the up-stream activation sequences from the yeast reporter gene, suggesting that the squelching interactions were with transcription factors needed for the activity of a basal promoter.
人们已经提出了一些DNA结合糖皮质激素受体反式激活基因表达的替代机制。糖皮质激素和其他类固醇激素受体在酵母中发挥作用这一事实表明，这些机制中至少有一种在整个进化过程中得到了保留。在这里，我们表明，酵母中糖皮质激素受体反式激活结构域之一（tau 1）的过表达会导致酵母报告基因的表达降低，随后酵母细胞的生长速率会严重降低。这类似于最初针对GAL4蛋白描述的抑制现象，表明糖皮质激素受体的tau 1结构域通过与有效基因活性所需的有限转录因子接触来发挥作用。从酵母报告基因中去除上游激活序列后，观察到了类似水平的抑制现象，这表明抑制相互作用是与基础启动子活性所需的转录因子发生的。
