Uemura H, Mizokami A, Chang C
Department of Human Oncology, University of Wisconsin, Madison 53792.
J Biol Chem. 1995 Mar 10;270(10):5427-33. doi: 10.1074/jbc.270.10.5427.
Human TR3 orphan receptor is a member of the steroid/thyroid hormone receptor superfamily and is the human homologue of the proteins encoded by the rat NGFI-B and mouse nur77 genes. These genes are induced rapidly by androgens/growth factors and may have functions related to cell proliferation, differentiation, and apoptosis. To investigate the TR3 orphan receptor gene transcriptional regulation, a 2.3-kilobase genomic DNA fragment containing the TR3 orphan receptor gene promoter region was isolated, sequenced, and characterized. Sequence homology search within this promoter region revealed some potential cis-acting elements such as cAMP response element, interleukin-6 response element, estrogen response element, and GC box. Deletion analysis and chloramphenicol acetyltransferase assay also showed a novel cis-acting element of TR3 orphan receptor gene (NCAE-TR3), 200-181 base pairs upstream of the transcriptional start site. Gel retardation assay further demonstrated that some nuclear factors can bind to this NCAE-TR3. Together, our data suggest that NCAE-TR3 could be a new enhancer element associated with the transcription of an early response gene for mitogenesis and apoptosis.
人类TR3孤儿受体是类固醇/甲状腺激素受体超家族的成员,是大鼠NGFI - B和小鼠nur77基因编码的蛋白质的人类同源物。这些基因可被雄激素/生长因子迅速诱导,可能具有与细胞增殖、分化和凋亡相关的功能。为了研究TR3孤儿受体基因的转录调控,分离、测序并鉴定了一个包含TR3孤儿受体基因启动子区域的2.3千碱基基因组DNA片段。在该启动子区域内进行的序列同源性搜索揭示了一些潜在的顺式作用元件,如cAMP反应元件、白细胞介素-6反应元件、雌激素反应元件和GC盒。缺失分析和氯霉素乙酰转移酶测定还显示了TR3孤儿受体基因的一个新的顺式作用元件(NCAE - TR3),位于转录起始位点上游200 - 18碱基对处。凝胶阻滞试验进一步证明一些一些一些核因子可与该NCAE - TR3结合。总之,我们的数据表明NCAE - TR3可能是一个与有丝分裂和凋亡早期反应基因转录相关的新增强子元件。