Dual regulatory effects of non-coding GC-rich elements on the expression of virulence genes in malaria parasites
Dual regulatory effects of non-coding GC-rich elements on the expression of virulence genes in malaria parasites
复制标题
富含GC的非编码元件对疟原虫毒力基因表达的双重调节作用
DOI：
10.1016/j.meegid.2015.08.023
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发表时间：
2015-12-01
影响因子：
3.2
通讯作者：
Pan，Weiqing
中科院分区：
文献类型：
--
作者：
Wei，Guiying;Zhao，Yuemeng;Pan，Weiqing
作为恶性疟原虫的主要毒力因子，vargenes具有相互排斥的表达模式，导致该病原体在人类宿主体内发生抗原变异和免疫逃避。尽管多种机制导致vargenes沉默，但对单个vargenes的转录激活途径以及与其他沉默varloci维持其活性状态的情况知之甚少。在这里，我们报告了染色体内部vargenes侧翼的非编码GC元件的单等位基因表达模式，并且在同一阵列中激活vargene需要来自活性元件的转录本。同时，GFP报告基因检测揭示了绝缘体样GC元件的DNA基序诱导的对邻近基因的抑制作用，这与异染色质亚核定位有关。总而言之，这些数据首次提供了 GC 元件在 vargenes 沉默和激活中的双重顺式和反式作用调节功能的实验证据，这将增进我们对 P 毒力基因家族复杂调节网络的理解。恶性疟原虫。
As the primary virulence factor offalciparummalaria,vargenes harboring mutually exclusive expression pattern lead to antigenic variation and immune evasion of this pathogen in human host. Although various mechanisms contribute to silence ofvargenes, little is known of transcriptional activation pathways of a singlevargene and maintenance of its active state with other silentvarloci. Here, we report a monoallelic expression pattern of the non-coding GC-elements flanking chromosomal internalvargenes, and transcript from the active one was required for activation of thevargene in the same array. Meanwhile, GFP reporter assays revealed a repressive effect on the adjacent gene induced by DNA motifs of the insulator-like GC-element, which was linked to heterochromatin subnuclear localization. Taken together, these data for the first time provide experimental evidence of the dualcis- andtrans-acting regulatory functions of the GC-elements in both silence and activation ofvargenes, which would advance our understanding of the complex regulatory network of the virulence gene family inP. falciparum.