Telomere Structure In Drosophila

工作概述：端粒是染色体末端的结构，是基因组稳定所必需的。果蝇的端粒缺乏大多数物种的简单重复序列。相反，果蝇的末端是通过一个非ltr反转录转座子家族HeT-A的尖端特异性转座来维持的。与末端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重复序列可能使其附近的基因失活，并与其他端粒形成关联。在许多情况下，当其他端粒是野生型时，TAS中的报告基因被抑制，但当任何其他端粒被插入TAS或TAS的缺失破坏时，其抑制较少。我们认为，端粒在TAS上相互关联，一个端粒的破坏给其他端粒上的反转录转座子发出转录信号，导致转基因周围的染色质松弛。一种依赖配对的转录因子zeste的突变破坏了这种相互作用，支持了端粒之间影响基因表达的物理相互作用的假设。这提供了一种机制来控制ht - a反转录转位，从而控制端粒伸长。在一个相关的项目中，正在对果蝇端粒抑制的反式作用抑制子进行表征。端粒沉默的抑制子映射到所有的主要染色体；其中一些是纯合致死的，这表明它们具有重要的功能。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的活性。它们对长期发育沉默也没有影响，这表明它们代表了一类新的染色体蛋白。抑制基因的突变表现出复杂的互补模式，表明编码的蛋白质形成了一个复合体来发挥作用。

Summary of Work: Telomeres are structures on the ends of chromosomes that are required for genome stability. Drosophila telomeres lack the simple repeats found 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 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 at TAS, and that disruption of one telomere signals the retrotransposons on other telomeres to transcribe, 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. This provides a mechanism to control HeT-A retrotransposition and thus telomere elongation. In a related project, trans-acting suppressers of telomeric repression in Drosophila are being characterized. Suppressers of telomeric silencing map to all the major chromosomes; several are homozygous lethal, suggesting they perform a vital functions. 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. Mutations in the suppressor genes show a complex complementation pattern, suggesting that the encoded proteins form a complex to function.