Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres
Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres
复制标题
DOI：
10.1038/sj.embor.7400575
复制
发表时间：
2006-01-01
期刊：
影响因子：
7.7
通讯作者：
Horn, D
中科院分区：
文献类型：
--
作者：
Glover, L;Horn, D
非洲锥虫（布氏锥虫）是一种有鞭毛的致病性原生动物，它在真核生物谱系中较早分化出来。不同寻常的是，它在血流型细胞中利用RNA聚合酶I（Pol I）进行变异表面糖蛋白（VSG）基因的单端粒表达。许多其他亚端粒VSG基因是可逆性抑制的，但在任何锥虫中都没有鉴定出抑制性DNA序列。在此，我们表明人工植入的新生端粒在布氏锥虫的哺乳动物血流和昆虫生命周期阶段抑制Pol I依赖的基因表达。在一个端粒VSG表达位点，抑制作用沿染色体进一步扩散，且这种效应是血流阶段所特有的。我们还表明新生端粒延伸是端粒酶依赖性的，并且延伸速率与相邻基因的表达水平相关。我们的研究结果显示布氏锥虫中存在组成性端粒抑制，并表明一种增强的、发育阶段特异性的抑制机制控制着抗原变异。
The African trypanosome, Trypanosoma brucei, is a flagellated pathogenic protozoan that branched early from the eukaryotic lineage. Unusually, it uses RNA polymerase I (Pol I) for monotelomeric expression of variant surface glycoprotein (VSG) genes in bloodstream-form cells. Many other subtelomeric VSG genes are reversibly repressed, but no repressive DNA sequence has been identified in any trypanosomatid. Here, we show that artificially seeded de novo telomeres repress Pol I-dependent gene expression in mammalian bloodstream and insect life-cycle stages of T. brucei. In a telomeric VSG expression site, repression spreads further along the chromosome and this effect is specific to the bloodstream stage. We also show that de novo telomere extension is telomerase dependent and that the rate of extension correlates with the expression level of the adjacent gene. Our results show constitutive telomeric repression in T. brucei and indicate that an enhanced, developmental stage-specific repression mechanism controls antigenic variation.