TELOMERE STRUCTURE IN DROSOPHILA

工作总结：端粒是线性染色体末端的结构，是基因组稳定所必需的。果蝇的端粒缺乏大多数物种端粒上的简单串联重复序列。相反，果蝇的末端是通过一个非LTR反转录转座子家族HET-A的末端特异性转座来维持的。与末端转座子阵列相邻的是一个端粒相关卫星(TAS)，它类似于其他物种的亚端粒序列。TAS重复序列可能使放置在其附近的基因失活，并与其他端粒形成关联。在果蝇中，放置在TAS中的报告基因受到抑制和多样化。在许多情况下，当其他端粒为野生型时，TAS中的报告基因受到抑制，但当任何其他端粒被插入TAS或缺失TAS打乱时，TAS中的报告基因受到的抑制较小。我们认为，就像在酵母中发现的那样，端粒相互关联，一个端粒的破坏向其他端粒上的反转录转座子发出信号，以转录HET-A，导致转基因周围的染色质松弛。ZEST是一种依赖配对的转录因子，它的突变破坏了这种相互作用，支持了端粒之间的物理相互作用影响基因表达的假说。诱导转录可促进HET-A逆转录转座和端粒伸长。在一个相关的项目中，已经分离出了54个果蝇端粒抑制的反式作用抑制因子，并正在对其进行鉴定。类似的着丝粒抑制修饰物以前被用来鉴定异染色质蛋白，但这些修饰物都没有对端粒抑制产生影响。端粒沉默的抑制子映射到所有的主要染色体；其中几个是纯合子致死的，这表明它们发挥着至关重要的功能。它们抑制插入各种端粒的基因的活性，但不抑制插入着丝粒异染色质的基因。它们对长期的发育沉默也没有影响，这表明它们代表了一种新的染色体蛋白质。

Summary of Work: Telomeres are structures on the ends of linear chromosomes that are required for genome stability. 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 family, HeT-A. Adjacent to the terminal transposon array is a telomere associated satellite (TAS) that resembles subtelomeric sequences in other species. The TAS repeats may inactivate genes placed in their vicinity, and form associations with other telomeres. In Drosophila, reporter genes placed in TAS are repressed and variegate. In many cases a reporter gene in TAS is repressed when the other telomeres are wild type, but less repressed when any other telomere is disrupted by an insertion into TAS or a deletion of TAS. We propose that the telomeres associate with each other, as has been found in yeast, and that disruption of one telomere signals the retrotransposons on other telomeres to transcribe HeT-A, resulting in relaxed chromatin around the transgene. Mutations of zeste, a pairing-dependent transcription factor, disrupt this interaction, supporting the hypothesis of physical interactions among telomeres affecting gene expression. The induced transcription may promote HeT-A retrotransposition and, telomere elongation. In a related project, 54 trans-acting suppressers of telomeric repression in Drosophila have been isolated and are being characterized. Similar modifiers of centromeric repression were used previously to identify heterochromatin proteins, but none of these has an effect on telomeric repression. Suppressers of telomeric silencing map to all the major chromosomes; several are homozygous lethal, suggesting they perform a vital function. They suppress the activity of genes inserted into various telomeres, but not genes inserted into centromeric heterochromatin. They also have no effect on long-term developmental silencing, suggesting that they represent a new class of chromosomal protein.