Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control.

Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control.
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DOI:
10.1111/cmi.12215
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发表时间:
2013-12
影响因子:
3.4
通讯作者:
Horn D
Horn D
中科院分区:
生物学2区
文献类型:
--
作者:
Glover L;Hutchinson S;Alsford S;McCulloch R;Field MC;Horn D

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非洲锥虫是一种致命的人类和动物寄生虫,它们利用抗原变异来逃避宿主的适应性免疫。为了促进抗原变异,锥虫大约三分之一的核基因组,包括许多微染色体,可能还有所有的亚端粒,都致力于表面糖蛋白(VSG)基因及其相关序列的变异。抗原变异需要通过RNA聚合酶I(Pol-I)转录单个VSG,同时沉默其他VSG,并周期性地切换表达的基因,通常是通过DNA重组和新的VSG复制易位到活性部位。因此,端粒定位、表观遗传控制和Pol-I在核外位点的单等位转录是VSGs及其表达的显著特征,端粒、染色质结构和核组织都对单等位VSG的表达控制和转换做出了至关重要的贡献。我们在染色体和亚核的背景下讨论了VSG的转录、重组和复制控制。
African trypanosomes are lethal human and animal parasites that use antigenic variation for evasion of host adaptive immunity. To facilitate antigenic variation, trypanosomes dedicate approximately one third of their nuclear genome, including many minichromosomes, and possibly all sub-telomeres, to variant surface glycoprotein (VSG) genes and associated sequences. Antigenic variation requires transcription of a single VSG by RNA polymerase I (Pol-I), with silencing of other VSGs, and periodic switching of the expressed gene, typically via DNA recombination with duplicative translocation of a new VSG to the active site. Thus, telomeric location, epigenetic controls and monoallelic transcription by Pol-I at an extranucleolar site are prominent features of VSGs and their expression, with telomeres, chromatin structure and nuclear organization all making vitally important contributions to monoallelic VSG expression control and switching. We discuss VSG transcription, recombination and replication control within this chromosomal and sub-nuclear context.
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