PfSET10, a Plasmodium falciparum methyltransferase, maintains the active var gene in a poised state during parasite division.
PfSET10, a Plasmodium falciparum methyltransferase, maintains the active var gene in a poised state during parasite division.
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DOI：
10.1016/j.chom.2011.11.011
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发表时间：
2012-01
影响因子：
30.3
通讯作者：
Jennifer C. Volz;R. Bártfai;Michaela Petter;Christine Langer;G. Josling;T. Tsuboi;F. Schwach;J. Baum;J. Rayner;H. Stunnenberg;M. Duffy;A. Cowman
中科院分区：
文献类型：
--
作者：
Jennifer C. Volz;R. Bártfai;Michaela Petter;Christine Langer;G. Josling;T. Tsuboi;F. Schwach;J. Baum;J. Rayner;H. Stunnenberg;M. Duffy;A. Cowman
红细胞膜蛋白1（PfEMP 1）是恶性疟原虫的一个主要毒力因子，它是一种表达于感染红细胞表面的变异蛋白。PfEMP 1负责感染的红细胞粘附到内皮细胞，并在发病机制中起重要作用。在每个寄生虫基因组中编码PfEMP 1的60个可变基因之一的互斥转录和转换表达提供了抗原变异的机制。我们报告的寄生虫蛋白，指定PfSET10，专门定位于核周activevargene表达位点的鉴定。PfSET 10是一种组蛋白3赖氨酸4甲基转移酶，在分裂过程中维持活化基因处于平衡状态，以便在子体寄生虫中重新活化，因此是恶性疟原虫抗原变异所必需的。PfSET10可能维持了活性启动子的转录允许的染色质环境，从而在寄生虫分裂期间保留了表观遗传信息的遗传传递记忆。
A major virulence factor of the malaria parasitePlasmodium falciparumiserythrocytemembraneprotein 1 (PfEMP1), a variant protein expressed on the infected erythrocyte surface. PfEMP1 is responsible for adherence of infected erythrocytes to the endothelium and plays an important role in pathogenesis. Mutually exclusive transcription and switched expression of one of 60vargenes encoding PfEMP1 in each parasite genome provides a mechanism for antigenic variation. We report the identification of a parasite protein, designated PfSET10, which localizes exclusively to the perinuclear activevargene expression site. PfSET10 is a histone 3 lysine 4 methyltransferase required to maintain the activevargene in a poised state during division for reactivation in daughter parasites, and as such is required forP. falciparumantigenic variation. PfSET10 likely maintains the transcriptionally permissive chromatin environment of the activevarpromoter and thus retains memory for heritable transmission of epigenetic information during parasite division.