SP1 & SP3 BINDING SITES & CAMP RESPONSIVE GH VARIANT TRANSCRIPTION: PLACENTA

目的：确定滋养层细胞特异性和 CAMP反应元件调节恒河猴转录 胎盘中的生长激素变异基因。结果人类和 非人灵长类胎盘表达了生长的一个独特成员 激素基因簇，胎盘生长激素变异(GH-V)。我们 希望进一步定义恒河猴GH-V转录 分化滋养层细胞的cAMP反应。基因突变的研究进展 GH-V基因启动子及随后的结合分析表明，Sp1和 SP3转录因子与启动子结合。核蛋白 分析证明了这些蛋白质的多种大小变体，以及 刺激GH-V转录的治疗对 这些蛋白质的水平或它们对结合元件的亲和力。 此外，Sp1和Sp3在绒毛组织中的免疫染色相似 胎盘组织中的细胞滋养细胞和合体滋养细胞。未来 方向我们将探讨后翻译的作用 刺激基因中预先存在的Sp1和Sp3蛋白的修饰 转录，我们将定义其他与DNA结合的蛋白质 与Sp1/Sp3位点相邻的序列。关键词胎盘，基因 转录，胎盘生长激素，转录因子

OBJECTIVE: To identify how trophoblast-specific and cAMP-responsive elements regulate transcription of the rhesus monkey growth hormone variant gene in the placenta. RESULTS The human and nonhuman primate placenta expresses a unique member of the growth hormone gene cluster, the placental growth hormone-variant (GH-V). We wished to further define rhesus monkey GH-V transcription which is cAMP-responsive in differentiated trophoblasts. Mutagenesis of the GH-V gene promoter and subsequent binding analysis showed that Sp1 and Sp3 transcription factors bind to the promoter. Nuclear protein analysis demonstrated multiple size variants of these proteins, and treatments which stimulate GH-V transcription have no effect on the levels of these proteins or their affinity for the binding elements. Additionally Sp1 and Sp3 immunostaining were similar in villous cytotrophoblasts and syncytiotrophoblasts in placental tissue. FUTURE DIRECTIONS We will explore both the role of post-translational modification of pre-existing Sp1 and Sp3 proteins in stimulating gene transcription, and we will define other protein binding to DNA sequences adjacent to the Sp1/Sp3 sites. KEY WORDS placenta, gene transcription, placental growth hormone, transcription factors