Structure of the rat gonadotropin releasing hormone (rGnRH) gene promoter and functional analysis in hypothalamic cells.
Structure of the rat gonadotropin releasing hormone (rGnRH) gene promoter and functional analysis in hypothalamic cells.
复制标题
大鼠促性腺激素释放激素（rGnRH）基因启动子的结构及下丘脑细胞的功能分析。
DOI：
10.1093/nar/20.6.1393
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发表时间：
1992
影响因子：
14.9
通讯作者：
M. Wierman
中科院分区：
文献类型：
--
作者：
J. Kepa;C. Wang;C. Neeley;M. Raynolds;D. Gordon;W. Wood;M. Wierman
促性腺激素释放激素（GnRH）基因编码的蛋白质在哺乳动物的生殖生理中起着关键作用。它的表达主要局限于下丘脑，虽然它也被描述在胎盘。为了开始确定组织特异性表达的重要启动子元件，并研究大鼠GnRH（rGnRH）基因的发育和激素调节机制，我们从大鼠肝脏基因组DNA文库中克隆了rGnRH基因。测定了大于3 kb的5 ′-侧翼区的核苷酸序列。用引物延伸分析法对大鼠下丘脑组织和小鼠下丘脑细胞系的转录起始位点进行了定位，发现它们存在差异。此外，瞬时转染研究表明，远端启动子的多个区域对于下丘脑细胞中的组织特异性和基础启动子活性是重要的。此外，在这些细胞中，在转录起始位点上游的-3026和-1031 bp之间存在有效的激活区，在-1031和-903 bp之间存在抑制区。我们的结论是，不同部分的5 '-侧翼区，这是激活和抑制的性质，是下丘脑表达的rGnRH基因的关键。
The gonadotropin releasing hormone (GnRH) gene encodes a protein which plays a critical role in mammalian reproductive physiology. Its expression is predominantly restricted to the hypothalamus although it has also been described in the placenta. To begin to determine the promoter elements important for tissue specific expression and to examine the mechanisms of developmental and hormonal regulation of the rat GnRH (rGnRH) gene, we cloned the rGnRH gene from a rat liver genomic DNA library. The nucleotide sequence of greater than 3 kb of 5'-flanking region was determined. The transcriptional initiation site in rat hypothalamic tissue and a mouse hypothalamic cell line were mapped by primer extension analysis and found to be different. In addition, transient transfection studies demonstrated that multiple regions of the distal promoter are important for tissue specific and basal promoter activity in hypothalamic cells. Furthermore, in these cells a potent activation region resides between -3026 and -1031 bp and suppressor region between -1031 and -903 bp upstream of the transcriptional start site. We conclude that different portions of the 5'-flanking region, which are activating and suppressing in nature, are critical for hypothalamic expression of the rGnRH gene.