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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. [ABSTRACT FROM AUTHOR]

Antunes et al. successfully grew cat-restricted stages of Toxoplasma gondii in cell culture by targeting parasite epigenetics and transcription factors. The highlight of this report is how efficiently parasites convert to these pre-sexual stages. Their work is an important step toward achieving feline-free recapitulation of the T. gondii sexual cycle. [ABSTRACT FROM AUTHOR]

Differentiation from asexual blood stages to mature sexual gametocytes is required for the transmission of malaria parasites. Here, we report that the ApiAP2 transcription factor, PfAP2‐G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2‐G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2‐G2 within the gene body of almost 3,000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2‐G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2‐g2 does not impact asexual development, but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2‐g2 leads to overexpression of 28% of the genes bound by PfAP2‐G2 and none of the PfAP2‐G2 bound genes are downregulated, suggesting that it is a repressor. We also find that PfAP2‐G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2‐G2 establishes an essential gametocyte maturation program in association with other chromatin‐related proteins. [ABSTRACT FROM AUTHOR]

The recent study by Campelo Morillo et al. has shown that one of the small number of non-ApiAP2 DNA-binding proteins in the Plasmodium falciparum genome acts as a transcription factor in the gametocytogenesis cascade and is responsible for the gametocyte's distinctive morphology. [ABSTRACT FROM AUTHOR]

Abstract: Malaria is caused by protozoan parasites of the genus Plasmodium and involves infection of multiple hosts and cell types during the course of an infection. To complete its complex life cycle the parasite requires strict control of gene regulation for survival and successful propagation. Thus far, the Apicomplexan AP2 (ApiAP2) family of DNA-binding proteins is the sole family of proteins to have surfaced as candidate transcription factors in all apicomplexan species. Work from several laboratories is beginning to shed light on how the ApiAP2 proteins from Plasmodium spp. contribute to the regulation of gene expression at various stages of parasite development. Here we highlight recent progress toward understanding the role of Plasmodium ApiAP2 proteins in DNA related regulatory processes including transcriptional regulation and gene silencing. [ABSTRACT FROM AUTHOR]