Analysis of the Molecular Mechanisms Governing the Stage-Specific Expression of a Prototypical Housekeeping Gene during Intraerythrocytic Development of P. falciparum
Analysis of the Molecular Mechanisms Governing the Stage-Specific Expression of a Prototypical Housekeeping Gene during Intraerythrocytic Development of P. falciparum
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DOI：
10.1016/j.jmb.2011.02.043
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发表时间：
2011-04-29
影响因子：
5.6
通讯作者：
Horrocks, Paul
中科院分区：
文献类型：
--
作者：
Wong, Eleanor H.;Hasenkamp, Sandra;Horrocks, Paul
人类恶性疟原虫红细胞内发育周期中的基因表达受到严格的时间控制，导致基因表达级联以满足生长、复制和再侵袭的生理需求。驱动这种基因表达时间程序的不同分子机制的作用知之甚少。在这里，我们报告使用的bxb1整合酶系统重建的绝对和时间控制的原型管家基因编码的增殖细胞核抗原（Pfpcna）周围的集成荧光素酶报告盒的所有方面。对5'和3'遗传元件的连续缺失和亚致死剂量的组蛋白去乙酰化酶抑制剂的影响的定量分析表明，虽然基因表达的绝对控制可能受到干扰，但没有观察到对基因表达的时间控制的影响。这些数据提供了一个新的模型，可能数百个基因的时间控制在红细胞内的发展，这一重要的人类病原体的支持。(C)2011爱思唯尔有限公司版权所有。
Gene expression during the intraerythrocytic development cycle of the human malarial parasite Plasmodium falciparum is subject to tight temporal control, resulting in a cascade of gene expression to meet the physiological demands of growth, replication, and reinvasion. The roles of the different molecular mechanisms that drive this temporal program of gene expression are poorly understood. Here we report the use of the bxb1 integrase system to reconstitute all aspects of the absolute and temporal control of the prototypical housekeeping gene encoding the proliferating cell nuclear antigen (Pfpcna) around an integrated luciferase reporter cassette. A quantitative analysis of the effect of the serial deletion of 5' and 3' genetic elements and sublethal doses of histone deacetylase inhibitors demonstrates that while the absolute control of gene expression could be perturbed, no effect on the temporal control of gene expression was observed. These data provide support for a novel model for the temporal control of potentially hundreds of genes during the intraerythrocytic development of this important human pathogen. (C) 2011 Elsevier Ltd. All rights reserved.