Estrogen stimulates estrogen-related receptor α gene expression through conserved hormone response elements
Estrogen stimulates estrogen-related receptor α gene expression through conserved hormone response elements
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DOI：
10.1210/en.2003-0432
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发表时间：
2003-11-01
期刊：
影响因子：
4.8
通讯作者：
Teng, CT
中科院分区：
文献类型：
--
作者：
Liu, DX;Zhang, ZP;Teng, CT
雌激素相关受体α基因编码核受体蛋白ERR α，其结构与雌激素受体密切相关。雌激素受体α（ERRalpha）对雌激素受体（ER）介导的信号传导通路具有正向和负向调节作用。它在发育过程中的多种细胞类型和成体组织中选择性表达。我们以前已经表明，雌激素刺激小鼠子宫的ERR α基因的表达。在本研究中，我们发现雌激素在小鼠子宫和心脏中刺激ERR α基因，但在肝脏中不刺激。雌激素还刺激人乳腺和子宫内膜细胞系中ERR α的表达。人ERR α基因启动子含有多个Sp1结合位点，Sp1蛋白是启动子活性所必需的。主要的雌激素反应是由一个34 bp的DNA元件介导的，该元件含有多个类固醇激素反应元件半位点（MHRE），这些半位点在人和小鼠ERR α基因启动子之间是保守的。在瞬时转染实验中，在MHRE的单个或多个位点进行的突变废除了ER介导的元件转录。通过染色质免疫沉淀分析，我们证明了在MCF-7细胞中内源性ERRa基因启动子的ERalpha和MHRE之间的相互作用。雌激素治疗进一步增强了ER α和MHRE在体内的关联。目前的研究表明，ERRa基因是ER α的下游靶点。
The estrogen-related receptor alpha gene encodes a nuclear receptor protein, ERRalpha, whose structure is closely related to the estrogen receptors. ERRalpha modulates estrogen receptor ( ER)mediated signaling pathways both positively and negatively. It is selectively expressed in a variety of cell types during development and in adult tissues. We have previously shown that estrogen stimulates the expression of the ERRalpha gene in mouse uterus. In this study, we found that the ERRalpha gene is stimulated by estrogen in mouse uterus and heart but not in liver. Estrogen also stimulates the expression of ERRalpha in the human breast and endometrial cell lines. The human ERRalpha gene promoter contains multiple Sp1 binding sites, and the Sp1 protein is required for the promoter activity. The major estrogen response is mediated by a 34-bp DNA element that contains multiple steroid hormone response element half-sites (MHREs) that are conserved between the human and mouse ERRalpha gene promoters. Mutations made at a single or multiple sites of the MHREs abolished the ER-mediated transcription of the element in transient transfection experiments. By chromatin immunoprecipitation assay, we demonstrated the interaction between ERalpha and MHREs of the endogenous ERRalpha gene promoter in MCF-7 cells. Estrogen treatment further enhanced the association of ERalpha and MHREs in vivo. The present study demonstrated that the ERRalpha gene is a downstream target of ERalpha.