Hess P, Meenakshi T, Chan G C, Carlstedt-Duke J, Gustafsson J A, Payvar F
E. A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104.
Proc Natl Acad Sci U S A. 1990 Apr;87(7):2564-8. doi: 10.1073/pnas.87.7.2564.
We have identified and characterized a 206-base-pair region downstream from rat alpha 2u-globulin promoter that specifically mediates a delayed secondary response to glucocorticoids. Unlike positive primary glucocorticoid response elements (GREs), this regulatory element, termed delayed sGRE, dictates an inductive process preceded by a time lag of several hours and blocked by the protein synthesis inhibitor cycloheximide. Reminiscent of GREs and negative GREs (nGREs), a delayed sGRE confers hormonal regulation upon a linked heterologous promoter from a downstream position with respect to transcription start site and, remarkably, also interacts selectively with purified glucocorticoid receptor. These results imply that receptor binding to a delayed sGRE in vivo may mediate certain secondary responses to glucocorticoid hormones.
我们已经鉴定并表征了大鼠α2u-球蛋白启动子下游一个206个碱基对的区域,该区域特异性介导对糖皮质激素的延迟二次应答。与阳性原发性糖皮质激素反应元件(GREs)不同,这个被称为延迟sGRE的调节元件决定了一个诱导过程,该过程之前有几个小时的时间延迟,并被蛋白质合成抑制剂环己酰亚胺阻断。与GREs和负性GREs(nGREs)类似,延迟sGRE从转录起始位点的下游位置赋予连接的异源启动子激素调节,并且值得注意的是,它还与纯化的糖皮质激素受体选择性相互作用。这些结果表明,体内受体与延迟sGRE的结合可能介导对糖皮质激素的某些二次应答。