TELOMERE STRUCTURE IN DROSOPHILA

工作概述：端粒是线性染色体末端的结构，是基因组稳定所必需的。它们抵消了由于DNA复制不完整而导致的染色体末端DNA的损失，并区分了自然染色体末端和断裂染色体末端。果蝇的端粒缺乏在大多数物种的端粒中发现的简单串联重复序列。相反，果蝇的末端是通过一个非ltr反转录转座子的尖端特异性转座来维持的。与该转座子阵列相邻的是端粒相关卫星（TAS），类似于其他物种的亚端粒序列。TAS重复序列被认为与异染色质的形成和其附近基因的失活有关，并可能有助于与其他端粒、核基质和层形成联系。放置在TAS中的报告基因受到抑制和多样性，即它们在适当组织的某些细胞中表达，而在其他细胞中不表达。在许多情况下，插入TAS的报告基因在同源物为野生型时受到极大的抑制，而在报告基因为纯合子时受到的抑制较少。当同源端粒被删除时，或当非同源端粒被插入到TAS中或被删除时，抑制也会减少。我们提出端粒在一个“端粒中心”中结合。位于端中心的报告基因受到抑制。通过插入其他非端粒基因或删除端粒中心的一个组成部分来破坏端粒中心，从而减轻这种抑制。已经分离出68个端粒抑制修饰因子，并对其进行了表征。类似的着丝点位置效应变异修饰因子已被用于鉴定异染色质蛋白，但这些修饰因子都不影响端粒位置效应。这表明一组新的端粒蛋白可能被提出的搜索确定。-染色体稳定性，异染色质，端粒，黑腹果蝇，基因表达调控

Summary of Work: Telomeres are structures on the ends of linear chromosomes that are required for genome stability. They counterbalance the loss of DNA from a chromosome end due to incomplete DNA replication and they distinguish a natural chromosome end from a broken chromosome end. Drosophila Telomeres lack the simple tandem repeats found at telomeres in most species. Instead, Drosophila ends are maintained by tip specific transposition of a non-LTR retrotransposon. Adjacent to this transposon array is a telomere associated satellite (TAS) that resembles subtelomeric sequences in other species. The TAS repeats are thought to be associated with the formation of heterochromatin and the inactivation of genes placed in their vicinity, and may be instrumental in forming associations with other telomeres, the nuclear matrix and the lamina. Reporter genes placed in TAS are repressed and variegate, that is they are expressed in some cells of the appropriate tissue, but not others. In many cases a reporter gene inserted into TAS is greatly repressed when the homologue is wild type, but less repressed when the reporter is homozygous. Decreased repression is also seen when the homologous telomere is deleted, or when a nonhomologous telomere is disrupted by an insertion into TAS or deleted. We propose that telomeres associate in a ?telocenter?, and that reporter genes placed in the telocenter are repressed. Disruption of the telocenter by insertion of other nontelomeric genes or deletion of one of the components of the telocenter relieves the repression. Sixty-eight transacting modifiers of telomeric repression have been isolated and are being characterized. Similar modifiers of centromeric position effect variegation have been used to identify heterochromatic proteins, but none of these modifiers have an effect on telomeric position effect. This suggests that a new set of telomeric proteins may be identified by the proposed search. - Chromosome Stability, Heterochromatin, Telomere, Drosophila Melanogaster, Gene Expression Regulation