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恶性疟原虫中的转录调控与基因沉默

Transcriptional control and gene silencing in Plasmodium falciparum.

作者信息

Coleman Bradley I, Duraisingh Manoj T

机构信息

Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.

出版信息

Cell Microbiol. 2008 Oct;10(10):1935-46. doi: 10.1111/j.1462-5822.2008.01203.x. Epub 2008 Jul 10.

DOI:10.1111/j.1462-5822.2008.01203.x
PMID:18637022
Abstract

Infection with the apicomplexan parasite Plasmodium falciparum is associated with a high burden of morbidity and mortality across the developing world, yet the mechanisms of transcriptional control in this organism are poorly understood. While P. falciparum possesses many of the characteristics common to eukaryotic transcription, including much of the canonical machinery, it also demonstrates unique patterns of gene expression and possesses unusually AT-rich intergenic sequences. Importantly, several biological processes that are critical to parasite virulence involve highly regulated patterns of gene expression and silencing. The relative scarcity of transcription-associated proteins and specific cis-regulatory motifs recognized in the P. falciparum genome have been thought to reflect a reduced role for transcription factors in transcriptional control in these parasites. New approaches and technologies, however, have led to the discovery of many more of these elements, including an expanded family of DNA-binding proteins, and a re-assessment of this hypothesis is required. We review the current understanding of transcriptional control in P. falciparum, specifically highlighting promoter-driven and epigenetic mechanisms involved in the control of transcription initiation.

摘要

感染顶复门寄生虫恶性疟原虫与发展中世界的高发病率和死亡率负担相关,但对该生物体中转录控制机制的了解却很少。虽然恶性疟原虫具有许多真核转录共有的特征,包括许多经典机制,但它也表现出独特的基因表达模式,并拥有异常富含AT的基因间序列。重要的是,对寄生虫毒力至关重要的几个生物学过程涉及高度调控的基因表达和沉默模式。恶性疟原虫基因组中公认的转录相关蛋白和特定顺式调控基序相对较少,这被认为反映了转录因子在这些寄生虫转录控制中的作用减弱。然而,新的方法和技术已导致发现了更多此类元件,包括一个扩展的DNA结合蛋白家族,因此需要重新评估这一假设。我们综述了目前对恶性疟原虫转录控制的理解,特别强调了参与转录起始控制的启动子驱动和表观遗传机制。

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