Ontology highlight
ABSTRACT:
PROVIDER: PRJNA990465 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25110700_1.fastq.gz | Fastqsanger.gz | |||
| SRR25110700_2.fastq.gz | Fastqsanger.gz | |||
| SRR25110701_1.fastq.gz | Fastqsanger.gz | |||
| SRR25110701_2.fastq.gz | Fastqsanger.gz | |||
| SRR25110702_1.fastq.gz | Fastqsanger.gz |
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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: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.
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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.
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Project description:Developmental regulation of the intracellular parasite Toxoplasma gondii is an understudied topic despite being central for a bid to control its dissemination around the globe. Of particular neglect are the factors that contribute to its sexual development. While it has previously been shown that generalized transcriptional repression machinery plays an important role in silencing spurious gene expression of sexually-committed parasites, the specific factors that target the generalized machinery to genetic loci remains unexplored. Here, we uncover that a member of the AP2 transcription factor family, AP2XII-2, is targeted to genomic loci that are associated with sexually-committed parasites along with the generalized regulators of transcriptional silencing, HDAC3 and MORC. Despite widespread association with gene promoters, AP2XII-2 is required for silencing of relatively few genes. We place two genes associated with sexual development downstream of AP2XII-2 control, transcription factor AP2X-10 and the amino acid hydroxylase AAH1. Dissecting gene regulatory pathways of Toxoplasma sexual development will likely be essential for controlling Toxoplasma dissemination in the future.
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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. 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, as revealed by mass spectrometry-based proteomic analyses of the parasites.
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Project description:Developmental regulation of the intracellular parasite Toxoplasma gondii is an understudied topic despite being central for a bid to control its dissemination around the globe. Of particular neglect are the factors that contribute to its sexual development. While it has previously been shown that generalized transcriptional repression machinery plays an important role in silencing spurious gene expression of sexually-committed parasites, the specific factors that target the generalized machinery to genetic loci remains unexplored. Here, we uncover that a member of the AP2 transcription factor family, AP2XII-2, is targeted to genomic loci that are associated with sexually-committed parasites along with the generalized regulators of transcriptional silencing, HDAC3 and MORC. Despite widespread association with gene promoters, AP2XII-2 is required for silencing of relatively few genes. We place two genes associated with sexual development downstream of AP2XII-2 control, transcription factor AP2X-10 and the amino acid hydroxylase AAH1. Dissecting gene regulatory pathways of Toxoplasma sexual development will likely be essential for controlling Toxoplasma dissemination in the future.
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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.
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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.
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