Oro A E, Hollenberg S M, Evans R M
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92138.
Cell. 1988 Dec 23;55(6):1109-14. doi: 10.1016/0092-8674(88)90255-3.
Binary developmental decisions and homeostatic regulation by steroids require negative transcriptional regulation to balance steroid-mediated stimulatory effects. Human glucocorticoid receptor mutants were used to identify regions important for trans-repression of the gene encoding the alpha subunit of chorionic gonadotropin. While the amino terminus is not critical, the DNA binding and ligand binding domains are required for efficient repression. However, the function of the carboxyl terminus can be substituted by a polypeptide from the human mineralocorticoid receptor or beta-galactosidase gene. The function of these fusion repressors supports the model that the human glucocorticoid receptor negatively regulates transcription via a steric hindrance mechanism. These results suggest a potentially general strategy for creation of sequence-specific transcriptional repressors.
类固醇的二元发育决策和稳态调节需要负转录调节来平衡类固醇介导的刺激作用。人类糖皮质激素受体突变体被用于鉴定对绒毛膜促性腺激素α亚基编码基因的反式抑制很重要的区域。虽然氨基末端并非至关重要，但DNA结合域和配体结合域对于有效抑制是必需的。然而，羧基末端的功能可以被来自人类盐皮质激素受体或β-半乳糖苷酶基因的多肽所取代。这些融合阻遏物的功能支持了人类糖皮质激素受体通过空间位阻机制负调节转录的模型。这些结果提示了一种创建序列特异性转录阻遏物的潜在通用策略。
