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

SP1

• 批准号: 6277650
• 负责人: THADDEUS G GOLOS
• 金额: $ 6.02万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277650
• 关键词: Primates; animal tissue; biotechnology; endocrine gland /system; genome; hormones; mother /infant health care; reproductive system

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

目的：确定滋养层细胞特异性和 cAMP反应元件调节恒河猴的转录 胎盘中的生长激素变异基因。 结果人和 非人灵长类胎盘表达了一种独特的生长因子 激素基因簇，胎盘生长激素变异体（GH-V）。 我们 希望进一步定义恒河猴GH-V转录， 在分化的滋养层中cAMP反应性。 诱变 GH-V基因启动子和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 分析表明这些蛋白质的多种大小变体， 刺激GH-V转录的处理对GH-V的表达没有影响。 这些蛋白质的水平或它们对结合元件的亲和力。 此外，在绒毛组织中，Sp1和Sp3的免疫染色相似， 胎盘组织中的细胞滋养层和合体滋养层。 未来 方向我们将探讨翻译后的作用， 刺激基因中预先存在的Sp1和Sp3蛋白的修饰 转录，我们将定义其他蛋白质结合到DNA 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