Cloning and characterization of the type I inositol 1,4,5-trisphosphate receptor gene promoter - Regulation by 17 beta-estradiol in osteoblasts
Cloning and characterization of the type I inositol 1,4,5-trisphosphate receptor gene promoter - Regulation by 17 beta-estradiol in osteoblasts
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DOI：
10.1074/jbc.272.36.22425
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发表时间：
1997-09-05
影响因子：
4.8
通讯作者：
Bradford, PG
中科院分区：
文献类型：
--
作者：
Kirkwood, KL;Homick, K;Bradford, PG
1，4，5-三磷酸肌醇（InsP（3））受体是胞内钙库释放信号和钙容性内流所必需的。我们分离了人I型InsP（3）受体基因的启动子和近端DNA片段，人6-292骨肉瘤和HL-60细胞的转录起始60个早幼粒细胞白血病细胞显示主要由位于共有TATA盒元件下游39个碱基对的腺嘌呤残基产生，当转染到6-292细胞中时，包括TATA盒的上游DNA促进氯霉素乙酰转移酶报告基因的定向转录，通过缺失作图和转录测定，鉴定了远端启动子中的负调控元件和近端区域中的正调控元件。近端区域响应于12-O-十四烷酰基佛波醇-13-乙酸酯或血清而增强转录，但响应于1，25-二羟维生素D-3或17 β-雌二醇。17 β-雌二醇的抑制作用由核雌激素受体介导，因为雌激素依赖性转录抑制被抗雌激素他莫昔芬和雌激素受体拮抗剂ICI 182，780抑制。这是首次对I型InsP（3）受体基因启动子进行研究，结果表明成骨细胞的慢性雌激素处理影响I型InsP（3）受体基因表达、信号转导和分泌的机制。
The inositol 1,4,5-trisphosphate (InsP(3)) receptor is essential for signal Ca2+ release from intracellular stores and for capacitative Ca2+ entry, We have isolated the promoter and proximal DNA segments of the human type I InsP(3) receptor gene, Transcription initiation in human 6-292 osteosarcoma and HL-60 promyelocytic leukemia cells was shown to occur predominantly from an adenine residue located 39 base pairs downstream of a consensus TATA box element, Upstream DNA including the TATA box promoted directional transcription of a chloramphenicol acetyltransferase reporter gene when transfected into 6-292 cells, A negative regulatory element in the distal promoter and a positive element in the proximal region were identified by deletion mapping and transcription assays, The proximal region enhanced transcription in response to 12-O-tetradecanoylphorbol-13-acetate or serum, but conferred transcriptional repression in response to 1,25-dihydroxyvitamin D-3 or 17 beta-estradiol. The repressive effect of 17 beta-estradiol was mediated by the nuclear estrogen receptor, as estrogen-dependent transcriptional repression was inhibited by the antiestrogen tamoxifen and the estrogen receptor antagonist ICI 182,780. This is the first study of the type I InsP(3) receptor gene promoter, and the results suggest a mechanism by which chronic estrogen treatment of osteoblasts affects type I InsP(3) receptor gene expression, signal transduction, and secretion.