Department of Medical Zoology, Mie University School of Medicine, Tsu City, Japan.
Department of Molecular Protozoology, Research Center for Infectious Disease Control, Osaka, Japan.
Elife. 2024 Jan 22;12:RP88317. doi: 10.7554/eLife.88317.
Gametocytes play key roles in the lifecycle. They are essential for sexual reproduction as precursors of the gametes. They also play an essential role in parasite transmission to mosquitoes. Elucidation of the gene regulation at this stage is essential for understanding these two processes at the molecular level and for developing new strategies to break the parasite lifecycle. We identified a novel transcription factor (TF), designated as a partner of AP2-FG or PFG. In this article, we report that this TF regulates the gene expression in female gametocytes in concert with another female-specific TF AP2-FG. Upon the disruption of , majority of female-specific genes were significantly downregulated, and female gametocyte lost the ability to produce ookinetes. ChIP-seq analysis showed that it was located in the same position as AP2-FG, indicating that these two TFs form a complex. ChIP-seq analysis of PFG in -disrupted parasites and ChIP-seq analysis of AP2-FG in -disrupted parasites demonstrated that PFG mediates the binding of AP2-FG to a ten-base motif and that AP2-FG binds another motif, GCTCA, in the absence of PFG. In promoter assays, this five-base motif was identified as another female-specific -acting element. Genes under the control of the two forms of AP2-FG, with or without PFG, partly overlapped; however, each form had target preferences. These results suggested that combinations of these two forms generate various expression patterns among the extensive genes expressed in female gametocytes.
配子体在生命周期中起着关键作用。它们是有性繁殖的必要条件，是配子的前体。它们在寄生虫向蚊子传播过程中也起着至关重要的作用。阐明这一阶段的基因调控对于从分子水平理解这两个过程以及开发打破寄生虫生命周期的新策略至关重要。我们鉴定了一种新的转录因子（TF），命名为 AP2-FG 或 PFG 的伴侣。在本文中，我们报告该 TF 与另一种雌性特异性 TF AP2-FG 一起调节雌性配子体中的基因表达。当 被破坏时，大多数雌性特异性基因的表达显著下调，雌性配子体丧失产生动合子的能力。ChIP-seq 分析表明它与 AP2-FG 位于相同位置，表明这两个 TF 形成复合物。在 被破坏的寄生虫中的 PFG 的 ChIP-seq 分析和在 被破坏的寄生虫中的 AP2-FG 的 ChIP-seq 分析表明，PFG 介导 AP2-FG 与十个碱基基序结合，并且在没有 PFG 的情况下，AP2-FG 结合另一个基序，GCTCA。在启动子测定中，该五个碱基基序被鉴定为另一个雌性特异性 - 作用元件。受两种形式的 AP2-FG 控制的基因，有或没有 PFG，部分重叠；然而，每种形式都有目标偏好。这些结果表明，这两种形式的组合在雌性配子体中广泛表达的基因中产生了各种表达模式。
