Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195-7280, USA.
Biochem Biophys Res Commun. 2010 Mar 19;393(4):603-8. doi: 10.1016/j.bbrc.2010.02.026. Epub 2010 Feb 10.
Precise spatial and temporal expression of the recently identified G-protein coupled receptor GPR54 is critical for proper reproductive function and metastasis suppression. However, regulatory factors that control GPR54 expression remain unknown. Thus, the identification of these cis-acting DNA elements can provide insight into the role of GPR54 in reproduction and cancer. Using luciferase reporter, electrophoretic mobility shift, and chromatin immunoprecipitation assays, we demonstrate that three SP1 sites and a partial estrogen response element modulate mouse GPR54 (mGPR54) promoter activity. Supporting experiments show transcription factor SP1 binds directly to the mGPR54 promoter region and activates gene expression. In conclusion, these novel findings now identify factors that regulate activity of the mGPR54 promoter, and these factors are highly conserved across multiple mammalian species.
最近发现的 G 蛋白偶联受体 GPR54 的精确时空表达对于正常的生殖功能和转移抑制至关重要。然而，控制 GPR54 表达的调节因子仍不清楚。因此，这些顺式作用 DNA 元件的鉴定可以深入了解 GPR54 在生殖和癌症中的作用。使用荧光素酶报告基因、电泳迁移率变动分析和染色质免疫沉淀实验，我们证明三个 SP1 位点和一个部分雌激素反应元件调节小鼠 GPR54（mGPR54）启动子活性。支持性实验表明转录因子 SP1 直接结合到 mGPR54 启动子区域并激活基因表达。总之，这些新发现现在确定了调节 mGPR54 启动子活性的因素，这些因素在多种哺乳动物物种中高度保守。
