PDF(Pubmed)
Abstract：
Toxoplasma gondii is an intracellular parasite that is important in medicine and veterinary science and undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have explored the role of the microrchidia (MORC) protein complex as a transcriptional suppressor of sexual commitment. By utilizing immunoprecipitation and mass spectrometry, constituents of this protein complex have been identified, including MORC, Histone Deacetylase 3 (HDAC3), and several ApiAP2 transcription factors. Conditional knockout of MORC or inhibition of HDAC3 results in upregulation of a set of genes associated with schizogony and sexual stages in T. gondii tachyzoites. Here, our focus extends to two primary ApiAP2s (AP2XII-1 and AP2XI-2), demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of AP2XII-1 and AP2XI-2 resulted in a profound alteration in merozoite-specific genes targeted by the MORC-HDAC3 complex. Additionally, considerable overlap was observed in downstream gene profiles between AP2XII-1 and AP2XI-2, with AP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including AP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by AP2XII-1 and AP2XI-2. This study provides valuable insights into the transcriptional regulation of T. gondii growth and development, shedding light on the intricate life cycle of this parasitic pathogen.
摘要：
弓形虫是一种细胞内寄生虫，在医学和兽医学中很重要，并且在其中间和最终宿主中经历了不同的发育转变。弓形虫阶段之间的切换受到各种因素的精心调节。先前的研究已经探索了微兰花（MORC）蛋白复合物作为性承诺的转录抑制因子的作用。利用免疫沉淀和质谱,这种蛋白质复合物的成分已经被鉴定，包括MORC,组蛋白去乙酰化酶3(HDAC3),和几个ApiAP2转录因子。MORC的条件敲除或HDAC3的抑制导致弓形虫速殖子中与分裂和性阶段相关的一组基因上调。这里,我们的重点扩展到两个主要的ApiAP2（AP2XII-1和AP2XI-2），证明它们对无性速殖子及其目标基因的适应性具有重大影响。值得注意的是,AP2XII-1和AP2XI-2的靶向破坏导致MORC-HDAC3复合物靶向的裂殖子特异性基因发生了深刻的变化。此外,在AP2XII-1和AP2XI-2之间的下游基因谱中观察到相当大的重叠，AP2XII-1特异性结合ApiAP2转录因子的子集，包括AP2XI-2。这些发现揭示了参与弓形虫分裂发育的ApiAP2调控网络的复杂级联，由AP2XII-1和AP2XI-2协调。这项研究为弓形虫生长发育的转录调控提供了有价值的见解，揭示了这种寄生虫的复杂生命周期。
