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首页> 外文期刊>Journal of Molecular Biology >Active transcription is required for maintenance of epigenetic memory in the malaria parasite Plasmodium falciparum.
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Active transcription is required for maintenance of epigenetic memory in the malaria parasite Plasmodium falciparum.

机译：维持疟原虫恶性疟原虫表观遗传记忆需要主动转录。

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摘要

The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. The primary antigenic and virulence determinant expressed on the surface of infected red blood cells is PfEMP1 (P. falciparum erythrocyte membrane protein 1), a protein that mediates adhesion and sequestration of the parasites in deep tissue vascular beds. Different forms of PfEMP1 are encoded by different members of the multicopy var gene family. Expression of var genes is mutually exclusive, and by switching which gene is expressed, parasites alter both their antigenic and virulence phenotypes. Regulation of var gene expression involves gene activation, silencing, and cellular memory, and the details of the mechanisms that control this process are not understood. Here, we provide evidence that active transcription is required for the maintenance of the cellular memory that marks a specific var gene to be stably expressed through numerous cell cycles. Forcing transfected parasites to express increasing numbers of unregulated episomal var promoters led to a corresponding down-regulation of the active var gene in the parasite's genome, presumably by competing for the transcriptional machinery of the parasite and suggesting the existence of a limited nuclear factor that is required for var gene activation. This process allowed us to repress transcription of the active var gene without acting through the mechanism that controls mutually exclusive expression and, thus, to investigate the role of transcription itself in maintaining epigenetic memory. When the competing episomes were removed, the parasites did not return to their previous var gene expression pattern, but rather displayed random var gene activation, demonstrating that the epigenetic imprint that controls var gene expression had been completely erased and, thus, linking active transcription to the maintenance of cellular memory.
机译：人类疟疾的最严重形式是由原生动物寄生虫恶性疟原虫引起的。在感染的红细胞表面表达的主要抗原和毒力决定因素是PfEMP1（恶性疟原虫红细胞膜蛋白1），该蛋白介导寄生虫在深层组织血管床中的粘附和隔离。不同形式的PfEMP1由多拷贝var基因家族的不同成员编码。 var基因的表达是互斥的，并且通过切换表达哪个基因，寄生虫会同时改变其抗原和毒力表型。 var基因表达的调控涉及基因激活，沉默和细胞记忆，并且尚不清楚控制该过程的机制的细节。在这里，我们提供的证据表明，需要主动转录来维持细胞记忆，这标志着特定的var基因要在众多细胞周期中稳定表达。强迫转染的寄生虫表达越来越多的不受调控的游离var启动子会导致该寄生虫基因组中活性var基因的相应下调，大概是通过竞争该寄生虫的转录机制并暗示存在有限的核因子，即var基因激活所需的。这个过程使我们能够抑制活性var基因的转录，而无需通过控制互斥表达的机制起作用，从而研究了转录本身在维持表观遗传记忆中的作用。当竞争的附加体被去除时，这些寄生虫并没有返回到其先前的var基因表达模式，而是表现出随机的var基因激活，表明控制var基因表达的表观遗传印记已被完全消除，因此将活性转录与维护手机内存。

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