Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: Expression site control from both ends?
Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: Expression site control from both ends?
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DOI：
10.1016/j.gene.2014.09.047
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发表时间：
2015-02-01
期刊：
影响因子：
3.5
通讯作者：
Park, Sung Hee
中科院分区：
文献类型：
--
作者：
Guenzl, Arthur;Kirkham, Justin K.;Park, Sung Hee
布氏锥虫是撒哈拉以南非洲人类和牲畜的一种媒介传播的致命原生生物寄生虫。其细胞表面涂层的抗原变异使寄生虫能够逃避适应性免疫反应，并在其哺乳动物宿主的血液中自由生活。外壳由一千万个变异表面糖蛋白（VSG）拷贝组成，该变异表面糖蛋白（VSG）由单个VSG基因表达，来自一个大的库，位于端粒附近的15个所谓的血流表达位点（BES）之一。因此，通过切换到不同VSG基因的表达来实现抗原变异。BES是表达位点相关基因和末端VSG基因的串联阵列。它由多功能RNA聚合酶I（RNAPI）从位于VSG基因上游45-60 kb的短启动子多顺反子转录。限制VSG表达到单个BES的机制还不清楚。有令人信服的证据表明，表观遗传沉默和转录衰减发挥重要作用。此外，最近的数据表明，在转录起始水平上存在调节，并且令人惊讶的是，VSG mRNA似乎在将VSG表达限制于单个基因中起作用。在这里，我们审查BES表达调控，并提出了一个模型，其中端粒定向，表观遗传BES沉默反对BES启动子定向，激活RNAPI转录。(C)2014爱思唯尔有限公司版权所有。
Trypanosoma brucei is a vector borne, lethal protistan parasite of humans and livestock in sub-Saharan Africa. Antigenic variation of its cell surface coat enables the parasite to evade adaptive immune responses and to live freely in the blood of its mammalian hosts. The coat consists of ten million copies of variant surface glycoprotein (VSG) that is expressed from a single VSG gene, drawn from a large repertoire and located near the telomere at one of fifteen so-called bloodstream expression sites (BESs). Thus, antigenic variation is achieved by switching to the expression of a different VSG gene. A BES is a tandem array of expression site-associated genes and a terminal VSG gene. It is polycistronically transcribed by a multifunctional RNA polymerase I (RNAPI) from a short promoter that is located 45-60 kb upstream of the VSG gene. The mechanism(s) restricting VSG expression to a single BES are not well understood. There is convincing evidence that epigenetic silencing and transcription attenuation play important roles. Furthermore, recent data indicated that there is regulation at the level of transcription initiation and that, surprisingly, the VSG mRNA appears to have a role in restricting VSG expression to a single gene. Here, we review BES expression regulation and propose a model in which telomere-directed, epigenetic BES silencing is opposed by BES promoter-directed, activated RNAPI transcription. (C) 2014 Elsevier B.V. All rights reserved.