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恶性疟原虫中染色质介导的表观遗传调控

Chromatin-mediated epigenetic regulation in the malaria parasite Plasmodium falciparum.

作者信息

Cui Liwang, Miao Jun

机构信息

Department of Entomology, Pennsylvania State University, 501 ASI Bldg., University Park, PA 16802, USA.

出版信息

Eukaryot Cell. 2010 Aug;9(8):1138-49. doi: 10.1128/EC.00036-10. Epub 2010 May 7.

DOI:10.1128/EC.00036-10
PMID:20453074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2918932/
Abstract

Malaria is a major public health problem in many developing countries, with the malignant tertian parasite Plasmodium falciparum causing the most malaria-associated mortality. Extensive research, especially with the advancement of genomics and transfection tools, has highlighted the fundamental importance of chromatin-mediated gene regulation in the developmental program of this early-branching eukaryote. The Plasmodium parasite genomes reveal the existence of both canonical and variant histones that make up the nucleosomes, as well as a full collection of conserved enzymes for chromatin remodeling and histone posttranslational modifications (PTMs). Recent studies have identified a wide array of both conserved and novel histone PTMs in P. falciparum, indicating the presence of a complex and divergent "histone code." Genome-wide analysis has begun to decipher the nucleosome landscape and histone modifications associated with the dynamic organization of chromatin structures during the parasite's life cycle. Focused studies on malaria-specific phenomena such as antigenic variation and red cell invasion pathways shed further light on the involvement of epigenetic mechanisms in these processes. Here we review our current understanding of chromatin-mediated gene regulation in malaria parasites, with specific reference to exemplar studies on antigenic variation and host cell invasion.

摘要

疟疾是许多发展中国家的一个主要公共卫生问题,恶性三日疟原虫导致了与疟疾相关的大部分死亡。广泛的研究,尤其是随着基因组学和转染工具的进步,凸显了染色质介导的基因调控在这种早期分支真核生物发育程序中的根本重要性。疟原虫基因组揭示了构成核小体的经典组蛋白和变体组蛋白的存在,以及用于染色质重塑和组蛋白翻译后修饰(PTM)的完整保守酶集合。最近的研究在恶性疟原虫中鉴定出了大量保守和新颖的组蛋白PTM,表明存在复杂且多样的“组蛋白密码”。全基因组分析已开始解读与寄生虫生命周期中染色质结构动态组织相关的核小体图谱和组蛋白修饰。对疟疾特异性现象如抗原变异和红细胞入侵途径的重点研究进一步揭示了表观遗传机制在这些过程中的作用。在此,我们综述了目前对疟原虫中染色质介导的基因调控的理解,并特别提及了关于抗原变异和宿主细胞入侵的典型研究。

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本文引用的文献

1
A major role for the Plasmodium falciparum ApiAP2 protein PfSIP2 in chromosome end biology.恶性疟原虫 ApiAP2 蛋白 PfSIP2 在染色体末端生物学中的主要作用。
PLoS Pathog. 2010 Feb 26;6(2):e1000784. doi: 10.1371/journal.ppat.1000784.
2
Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.组蛋白去乙酰化酶在疟原虫生命周期的转录调控中起主要作用。
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Epigenetic control of the variable expression of a Plasmodium falciparum receptor protein for erythrocyte invasion.疟原虫入侵红细胞的受体蛋白可变表达的表观遗传控制。
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2224-9. doi: 10.1073/pnas.0913396107. Epub 2010 Jan 13.
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Nucleosome landscape and control of transcription in the human malaria parasite.人类疟原虫中的核小体景观和转录调控。
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5
Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes.疟原虫全基因组核小体作图揭示富含组蛋白的编码区和组蛋白贫乏的基因间区,以及核心和端粒下基因的染色质重塑。
BMC Genomics. 2009 Dec 16;10:610. doi: 10.1186/1471-2164-10-610.
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Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites.个体疟原虫寄生虫中重复 var2csa 基因副本的同时转录。
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7
Potential epigenetic regulatory proteins localise to distinct nuclear sub-compartments in Plasmodium falciparum.疟原虫中潜在的表观遗传调控蛋白定位于不同的核亚区室。
Int J Parasitol. 2010 Jan;40(1):109-21. doi: 10.1016/j.ijpara.2009.09.002. Epub 2009 Sep 16.
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Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.恶性疟原虫异染色质蛋白1标记与输出毒力因子表型变异相关的基因组位点。
PLoS Pathog. 2009 Sep;5(9):e1000569. doi: 10.1371/journal.ppat.1000569. Epub 2009 Sep 4.
9
Clonally variant gene families in Plasmodium falciparum share a common activation factor.恶性疟原虫中的克隆变异基因家族共享一个共同的激活因子。
Mol Microbiol. 2009 Sep;73(6):1171-85. doi: 10.1111/j.1365-2958.2009.06846.x. Epub 2009 Aug 24.
10
The effect of Plasmodium falciparum Sir2a histone deacetylase on clonal and longitudinal variation in expression of the var family of virulence genes.恶性疟原虫 Sir2a 组蛋白去乙酰化酶对 var 家族毒力基因表达的克隆和纵向变异的影响。
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