Jantzen H M, Strähle U, Gloss B, Stewart F, Schmid W, Boshart M, Miksicek R, Schütz G
Cell. 1987 Apr 10;49(1):29-38. doi: 10.1016/0092-8674(87)90752-5.
Two glucocorticoid response elements (GREs) located 2.5 kb upstream of the transcription initiation site of the tyrosine aminotransferase gene were identified by gene transfer experiments and shown to bind to purified glucocorticoid receptor. Although the proximal GRE has no inherent capacity by itself to stimulate transcription, when present in conjunction with the distal GRE, this element synergistically enhances glucocorticoid induction of gene expression. Cooperativity of the two GREs is maintained when they are transposed upstream of a heterologous promoter. An oligonucleotide of 22 bp representing the distal GRE is sufficient to confer glucocorticoid inducibility. As evidenced by the mapping of DNAase I hypersensitive sites, local alterations in the structure of chromatin at the GREs take place as a consequence of hormonal treatment.
通过基因转移实验,在酪氨酸转氨酶基因转录起始位点上游2.5 kb处鉴定出两个糖皮质激素反应元件(GREs),并证明它们能与纯化的糖皮质激素受体结合。虽然近端GRE本身没有刺激转录的内在能力,但当与远端GRE同时存在时,该元件能协同增强糖皮质激素诱导的基因表达。当两个GREs转位到异源启动子上游时,它们之间的协同作用得以维持。一个代表远端GRE的22 bp寡核苷酸足以赋予糖皮质激素诱导性。如DNA酶I超敏位点图谱所示,激素处理导致GREs处染色质结构发生局部改变。