Ontology highlight
ABSTRACT:
PROVIDER: PRJNA990966 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Commitment to and completion of sexual development are essential for Toxoplasma gondii to produce oocysts in the intestine of the feline host. Understanding of the molecular mechanism responsible for sexual commitment is extremely limited due to the lack of model systems. Here, we show that the transcription factors AP2XI-2 and AP2XII-1 associated with the epigenetic repressors MORC/HDAC3 complex are constitutively expressed in both tachyzoite and bradyzoite stages but not in the merozoite stage. Depletion of AP2XI-2 or AP2XII-1 elicits the expression of genes specific to merozoites, but they play different roles in the merogony process. Depletion of AP2XI-2 in type II Pru strain induced parasites to undergo merogony and produce mature merozoites in alkaline medium but not in neutral medium, whereas the AP2XII-1 depleted Pru strain underwent several rounds of schizogony and produced merozoites in neutral medium and more markedly under alkaline conditions. Furthermore, we show that two AP2XI-2 interacting proteins are also involved in repressing merozoite programming. Overall, these findings indicate that the merozoite primed pre-sexual commitment is controlled by an intricate regulatory network and that AP2XI-2 or AP2XII-1 depleted parasites can be used as a model to study the merogony in vitro.
2023-12-19 | GSE248448 | GEO
Project description:Here we show that AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites. Pre-gametes produced in vitro are characterized by specific protein markers and undergo typical asexual endopolygenic division cycles. AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit the epigenitors MORC and HDAC3, which in turn restrict the accessibility of chromatin to the transcriptional machinery.
2023-09-16 | GSE222819 | GEO
Project description:Here we show that AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites. Pre-gametes produced in vitro are characterized by specific protein markers and undergo typical asexual endopolygenic division cycles. AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit the epigenitors MORC and HDAC3, which in turn restrict the accessibility of chromatin to the transcriptional machinery.
2023-09-16 | GSE222832 | GEO
Project description:Commitment to and completion of sexual development are essential for Toxoplasma gondii to produce oocysts in the intestine of the feline host. Understanding of the molecular mechanism responsible for sexual commitment is extremely limited due to the lack of model systems. Here, we show that the transcription factors AP2XI-2 and AP2XII-1 associated with the epigenetic repressors MORC/HDAC3 complex are constitutively expressed in both tachyzoite and bradyzoite stages but not in the merozoite stage. Depletion of AP2XI-2 or AP2XII-1 elicits the expression of genes specific to merozoites, but they play different roles in the merogony process. Depletion of AP2XI-2 in type II Pru strain induced parasites to undergo merogony and produce mature merozoites in alkaline medium but not in neutral medium, whereas the AP2XII-1 depleted Pru strain underwent several rounds of schizogony and produced merozoites in neutral medium and more markedly under alkaline conditions. Furthermore, we show that two AP2XI-2 interacting proteins are also involved in repressing merozoite programming. Overall, these findings indicate that the merozoite primed pre-sexual commitment is controlled by an intricate regulatory network and that AP2XI-2 or AP2XII-1 depleted parasites can be used as a model to study the merogony in vitro.
2023-12-20 | PXD043808 | Pride
Project description:Toxoplasma proliferation is governed by its flexible but tightly regulated cell division cycle, that remarkably depends on appropriate and temporal transcriptional waves throughout the division cycle although the underlying regulation network is still unclear. Here we reported the transcriptional factor, AP2XI-3, as an essential cell cycle related gene regulator in G1 progression. After AP2XI-3 depletion, tachyzoites growth was obviously arrested in G1 phage and daughter budding progression was also destroyed. Intriguingly, the growth arrest of mutant parasites was also observed in vitro. Combining analysis of RNA sequencing and Cut & TAG revealed the key regulatory role of AP2XI-3 in G1 phage related biomass accumulation and cellular competent. AP2XI-3 controlled and targeted a set of RNA transcription, metabolism or protein biosynthesis related genes, whose dysregulation functionally disrupted cell homeostasis and parasite division. Altogether, our finding demonstrated the functional role of AP2XI-3 in transcriptional controlling of G1 progression and revealed its potential ability as a drug design target.
2026-01-01 | GSE285354 | GEO
Project description:Toxoplasma proliferation is governed by its flexible but tightly regulated cell division cycle, that remarkably depends on appropriate and temporal transcriptional waves throughout the division cycle although the underlying regulation network is still unclear. Here we reported the transcriptional factor, AP2XI-3, as an essential cell cycle related gene regulator in G1 progression. After AP2XI-3 depletion, tachyzoites growth was obviously arrested in G1 phage and daughter budding progression was also destroyed. Intriguingly, the growth arrest of mutant parasites was also observed in vitro. Combining analysis of RNA sequencing and Cut & TAG revealed the key regulatory role of AP2XI-3 in G1 phage related biomass accumulation and cellular competent. AP2XI-3 controlled and targeted a set of RNA transcription, metabolism or protein biosynthesis related genes, whose dysregulation functionally disrupted cell homeostasis and parasite division. Altogether, our finding demonstrated the functional role of AP2XI-3 in transcriptional controlling of G1 progression and revealed its potential ability as a drug design target.
2026-01-01 | GSE304633 | GEO
Project description:Toxoplasma proliferation is governed by its flexible but tightly regulated cell division cycle, that remarkably depends on appropriate and temporal transcriptional waves throughout the division cycle although the underlying regulation network is still unclear. Here we reported the transcriptional factor, AP2XI-3, as an essential cell cycle related gene regulator in G1 progression. After AP2XI-3 depletion, tachyzoites growth was obviously arrested in G1 phage and daughter budding progression was also destroyed. Intriguingly, the growth arrest of mutant parasites was also observed in vitro. Combining analysis of RNA sequencing and Cut & TAG revealed the key regulatory role of AP2XI-3 in G1 phage related biomass accumulation and cellular competent. AP2XI-3 controlled and targeted a set of RNA transcription, metabolism or protein biosynthesis related genes, whose dysregulation functionally disrupted cell homeostasis and parasite division. Altogether, our finding demonstrated the functional role of AP2XI-3 in transcriptional controlling of G1 progression and revealed its potential ability as a drug design target.
2026-01-01 | GSE285353 | GEO
Project description:Sexual reproduction of Toxoplasma gondii, which is restricted to the small intestine of felids, is sparsely documented in studies involving domestic cats, which also raises ethical concerns. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites. AP2XI-2 and AP2XII-1 likely synergize to suppress gene expression in tachyzoites, but their modus operandi is still enigmatic. We therefore characterized their interactomes.
2023-09-16 | PXD042658 | Pride
Project description:AP2XI-3 binding sites in Toxoplasma gondii [CUT&Tag]
| PRJNA1203222 | ENA