Toxoplasma gondii AP2XII-2 Contributes to Transcriptional Repression for Sexual Commitment.
Toxoplasma gondii AP2XII-2 Contributes to Transcriptional Repression for Sexual Commitment.
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弓形虫是一种广泛分布的原生动物寄生虫，对人类和兽医的健康具有重大影响。该寄生虫经历了涉及多个宿主和发育阶段的复杂生命周期。人们对弓形虫如何在生命周期阶段之间转变知之甚少，但对于控制传播至关重要。特别被忽视的是有助于性发育的因素，性发育仅发生在猫科动物的肠道中。虽然表观遗传抑制因子已被证明在沉默有性寄生虫的虚假基因表达方面发挥着重要作用，但将这种通用机制招募到适当基因的具体因素在很大程度上仍未被探索。在此，我们确定 AP2 转录因子家族的成员 AP2XII-2 靶向与性寄生寄生虫相关的基因组位点以及转录沉默的表观遗传调节因子 HDAC3 和 MORC。尽管 AP2XII-2 与基因启动子广泛相关，但它是沉默相对较少基因所必需的。使用 CUT&Tag（目标下切割和标记）方法，我们确定了 AP2XII-2 控制下游与性发育相关的两个主要基因：AP2X-10 和氨基酸羟化酶 AAH1。我们的研究结果表明 AP2XII-2 是调节弓形虫性发育的基因调控途径的关键贡献者。重要性 弓形虫是一种寄生虫，仅在猫科动物的肠道中经历有性阶段，使猫成为主要传播源。为了开发旨在治疗弓形体病和感染传播的新疗法，需要更好地了解控制寄生虫生命周期阶段转变的蛋白质。调节性阶段的基因需要在适当的时间打开和关闭，这些活动是由特定转录因子介导的，这些转录因子招募通用机制来沉默或激活基因表达。在这项研究中，我们确定了一种名为 AP2XII-2 的转录因子，它对于抑制性阶段基因的子集非常重要，其中包括性阶段特异性 AP2 因子 (AP2X-10) 和构建从受感染猫排出的传染性卵囊所需的蛋白质 (AAH1)。
Toxoplasma gondii is a widespread protozoan parasite that has a significant impact on human and veterinary health. The parasite undergoes a complex life cycle involving multiple hosts and developmental stages. How Toxoplasma transitions between life cycle stages is poorly understood yet central to controlling transmission. Of particular neglect are the factors that contribute to its sexual development, which takes place exclusively in feline intestines. While epigenetic repressors have been shown to play an important role in silencing the spurious gene expression of sexually committed parasites, the specific factors that recruit this generalized machinery to the appropriate genes remain largely unexplored. Here, we establish that a member of the AP2 transcription factor family, AP2XII-2, is targeted to genomic loci associated with sexually committed parasites along with epigenetic regulators of transcriptional silencing, HDAC3 and MORC. Despite its widespread association with gene promoters, AP2XII-2 is required for the silencing of relatively few genes. Using the CUT&Tag (cleavage under targets and tagmentation) methodology, we identify two major genes associated with sexual development downstream of AP2XII-2 control, AP2X-10 and the amino acid hydroxylase AAH1. Our findings show that AP2XII-2 is a key contributor to the gene regulatory pathways modulating Toxoplasma sexual development. IMPORTANCE Toxoplasma gondii is a parasite that undergoes its sexual stage exclusively in feline intestines, making cats a major source of transmission. A better understanding of the proteins controlling the parasite’s life cycle stage transitions is needed for the development of new therapies aimed at treating toxoplasmosis and the transmission of the infection. Genes that regulate the sexual stages need to be turned on and off at the appropriate times, activities that are mediated by specific transcription factors that recruit general machinery to silence or activate gene expression. In this study, we identify a transcription factor called AP2XII-2 as being important for the repression of a subset of sexual stage genes, including a sexual stage-specific AP2 factor (AP2X-10) and a protein (AAH1) required to construct the infectious oocysts expelled from infected cats.