TRANSCRIPTIONAL REGULATION OF THE MYELIN PROTEOLIPID PROTEIN GENE

髓磷脂蛋白脂蛋白基因的转录调控

• 批准号: 7959429
• 负责人: BRIAN T GREUEL
• 金额: $ 8.29万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959429
• 关键词: Arkansas; Axon; Biomedical Research; Cell Line; Cells; Computer Retrieval of Information on Scientific Projects Database; Elements; Enhancers; Funding; Gene Expression; Genes; Genetic Enhancer Element; Grant; Institution; Introns; Link; Mammals; Mediating; Mus; Myelin Proteolipid Protein; Neuraxis; Neurons; Oligodendroglia; Regulation; Regulatory Element; Reporter Genes; Research; Research Personnel; Resources; Series; Source; Testing; Testis; Transcriptional Regulation; United States National Institutes of Health; cell type; leydig interstitial cell; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Expression of the myelin proteolipid protein (Plp) gene in mammals is intimately tied to the differentiation of oligodendrocytes and reaches a peak during the period in which these cells are actively myelinating the axons of neurons in the central nervous system. Low-level expression of the Plp gene has also been detected in several non-oligodendroglial cell types, including the Leydig cells of the testis, but the functional significance of this expression has yet to be determined. Several regulatory elements/regions, located within the first intron of the Plp gene, have been implicated in the spatial and temporal regulation of Plp gene expression. One of these elements, designated the antisilencer/enhancer (ASE), appears to mediate a dramatic upsurge in Plp gene expression in oligodendrocytes by counteracting the effects of negative regulatory elements located within the first intron. One possible explanation for the lower level of Plp expression in non-oligodendroglial cells is that the ASE is much less active in these cells and is relatively ineffective in counteracting the negative regulatory elements. To test this hypothesis, we analyzed the effects of a series of Plp intron 1 deletions on the expression of a linked reporter gene (lacZ) in a transiently transfected mouse Leydig cell line (TM3). The results of these experiments confirmed that the ASE element/region of Plp intron 1 has minimal activity in Leydig cells, while general and cell type specific negative regulatory elements within the intron are very active in repressing expression of the reporter gene. Preliminary evidence also suggests that a positive regulatory element located near the 5 end of the intron, and distinct from the ASE, may function specifically in Leydig cells. This issue will be explored in more depth by looking at the effects of additional deletions near the 5 end of the intron. (to start June 1, 2004)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在哺乳动物中，髓鞘蛋白脂蛋白(PLP)基因的表达与少突胶质细胞的分化密切相关，并在这些细胞活跃地将中枢神经系统中的神经元轴突髓鞘化时达到高峰。在包括睾丸间质细胞在内的几种非少突胶质细胞中也检测到PLP基因的低水平表达，但这种表达的功能意义尚未确定。位于PLP基因第一内含子内的几个调控元件/区域参与了PLP基因表达的时空调控。其中一个被命名为抗沉默/增强子(ASE)的元件，似乎通过抵消位于第一内含子内的负调控元件的作用来调节少突胶质细胞中PLP基因表达的急剧上升。非少突胶质细胞中PLP表达水平较低的一个可能解释是，ASE在这些细胞中的活性要低得多，在对抗负调控元件方面相对无效。为了验证这一假说，我们分析了一系列PLP内含子1缺失对瞬时转基因小鼠间质细胞系(TM3)中连锁报告基因(LacZ)表达的影响。这些实验结果证实，PLP内含子1的酶元件/区域在间质细胞中活性最低，而内含子内的一般和细胞类型特异的负调控元件在抑制报告基因的表达方面非常活跃。初步证据还表明，位于内含子5端附近的一个不同于ASE的正调控元件可能在间质细胞中特异发挥作用。将通过研究内含子5末端附近额外缺失的影响来更深入地探讨这一问题。 (2004年6月1日开始)