Pace Tomasino, Olivieri Anna, Sanchez Massimo, Albanesi Veronica, Picci Leonardo, Siden Kiamos Inga, Janse Chris J, Waters Andrew P, Pizzi Elisabetta, Ponzi Marta
Dipartimento di Malattie Infettive Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
Mol Microbiol. 2006 May;60(4):870-82. doi: 10.1111/j.1365-2958.2006.05141.x.
Transmission of the malaria parasite depends on specialized gamete precursors (gametocytes) that develop in the bloodstream of a vertebrate host. Gametocyte/gamete differentiation requires controlled patterns of gene expression and regulation not only of stage and gender-specific genes but also of genes associated with DNA replication and mitosis. Once taken up by mosquito, male gametocytes undergo three mitotic cycles within few minutes to produce eight motile gametes. Here we analysed, in two Plasmodium species, the expression of SET, a conserved nuclear protein involved in chromatin dynamics. SET is expressed in both asexual and sexual blood stages but strongly accumulates in male gametocytes. We demonstrated functionally the presence of two distinct promoters upstream of the set open reading frame, the one active in all blood stage parasites while the other active only in gametocytes and in a fraction of schizonts possibly committed to sexual differentiation. In ookinetes both promoters exhibit a basal activity, while in the oocysts the gametocyte-specific promoter is silent and the reporter gene is only transcribed from the constitutive promoter. This transcriptional control, described for the first time in Plasmodium, provides a mechanism by which single-copy genes can be differently modulated during parasite development. In male gametocytes an overexpression of SET might contribute to a prompt entry and execution of S/M phases within mosquito vector.
疟原虫的传播依赖于在脊椎动物宿主血液中发育的特殊配子前体（配子体）。配子体/配子的分化需要基因表达和调控的可控模式，这不仅涉及阶段和性别特异性基因，还包括与DNA复制和有丝分裂相关的基因。一旦被蚊子摄取，雄配子体在几分钟内经历三个有丝分裂周期，产生八个可运动的配子。在这里，我们分析了两种疟原虫中SET的表达，SET是一种参与染色质动态变化的保守核蛋白。SET在无性和有性血液阶段均有表达，但在雄配子体中大量积累。我们在功能上证明了set开放阅读框上游存在两个不同的启动子，一个在所有血液阶段的寄生虫中都有活性，而另一个仅在配子体和一部分可能致力于性分化的裂殖体中有活性。在动合子中，两个启动子都表现出基础活性，而在卵囊中，配子体特异性启动子沉默，报告基因仅从组成型启动子转录。这种转录调控首次在疟原虫中被描述，它提供了一种机制，通过该机制单拷贝基因在寄生虫发育过程中可以受到不同的调节。在雄配子体中，SET的过表达可能有助于在蚊媒中迅速进入并执行S/M期。
