AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1047515 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR27011421_1.fastq.gz | Fastqsanger.gz | |||
| SRR27011421_2.fastq.gz | Fastqsanger.gz | |||
| SRR30811158_1.fastq.gz | Fastqsanger.gz | |||
| SRR30811158_2.fastq.gz | Fastqsanger.gz |
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Project description:Toxoplasma gondii is a ubiquitous protozoan with a complex life cycle involving transitions between different hosts and developmental stages, each adapted to a unique niche within its host. However, the regulatory mechanisms controlling these life cycle transitions remain poorly understood. In this study, we characterized the AP2 factor AP2X-1, which is expressed during the tachyzoite and bradyzoite stages, but not in the mature merozoite stage. Knockout of ap2X-1 significantly impaired tachyzoite invasion and replication, while increasing the frequency of bradyzoite differentiation. As a component of the HDAC3/MORC complex, knockout of ap2X-1 led to the upregulation of bradyzoite and sexual stage-specific genes. Single-cell sequencing revealed that ap2X-1 knockout strains behaved as a mixed population of tachyzoites, bradyzoites, merozoites, and sporozoites. CUT&Tag analysis revealed substantial overlap between AP2X-1 and HDAC3/MORC complex binding at the promoters of bradyzoite and sexual stage-specific genes. Additionally, ATAC-seq analysis demonstrated that AP2X-1 modulates chromatin compaction and accessibility, suggesting that AP2X-1 recruits the HDAC3/MORC complex to repress bradyzoite differentiation and sexual commitment. The loss of ap2X-1 resulted in significant attenuation of T. gondii virulence and reduced the formation of brain cysts in vivo. These findings identify AP2X-1 as a critical negative regulator of T. gondii sexual development.
2025-06-25 | GSE249123 | GEO
Project description:Toxoplasma gondii is a widespread protozoan with a complex life cycle, characterized by transitions between various hosts and developmental stages, each tailored to a specific niche within its host. However, the regulatory mechanisms governing these life cycle transitions are not well understood. In this study, we investigated the AP2 factor AP2X-1, which is expressed during the tachyzoite and bradyzoite stages but decreases in the mature merozoite stage. Knockout of ap2X-1 significantly impaired tachyzoite invasion and replication while increasing the frequency of bradyzoite differentiation. As a component associated with the HDAC3/MORC complex, loss of ap2X-1 led to the upregulation of bradyzoite- and sexual stage-specific genes. Single-cell sequencing revealed that ap2X-1 knockout strain exhibited a mixed population of tachyzoite-, bradyzoite-, merozoite-, and sporozoite-like parasites. CUT&Tag analysis revealed a substantial overlap between AP2X-1 and HDAC3/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes. Additionally, ATAC-seq analysis demonstrated that AP2X-1 influences chromatin compaction and accessibility, suggesting that AP2X-1 may modulate the function of the HDAC3/MORC complex to facilitate the repression of bradyzoite differentiation and sexual commitment. Loss of ap2X-1 resulted in a significant attenuation of T. gondii virulence and decreased brain cyst formation in vivo. These findings identify AP2X-1 as a critical negative regulator of T. gondii sexual development.
2025-06-29 | PXD065585 | Pride
Project description:Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.
2019-12-21 | GSE136060 | 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.
2023-12-19 | 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.
2023-12-20 | PXD043808 | Pride
Project description:Purpose: T. gondii has a complex life cycle typified by an asexual development taking place in vertebrate and a sexual reproduction occurring exclusively in felids and thereby is less studied. The developmental transitions rely on changes in gene expression patterns, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific programs for a given stage. Here, we identified T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in partnership with Apetala (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the chromatin accessibility of the genes predestined to be exclusively expressed in sexual stages. As such, MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, thus revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 factors, with these latter potentially contributing to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a way to study the parasite’s sexual development in vitro, and proposes an alternative to the requirement of cat infections.
2019-12-21 | GSE136123 | GEO
Project description:Recent advances in high throughput sequencing methodologies allow the opportunity to probe in depth the transcriptomes of organisms including N. caninum and Toxoplasma gondii. In this project, we are using Illumina sequencing technology to analyze the transcriptome (RNA-Seq) of experimentally accessible stages (e.g. tachyzoites at different times points) of T. gondii VEG strain. The aim is to make comparative transcriptional landscape maps of Neospora and Toxoplasma at different time points at different life cycle stages and compare levels of expression of orthologous genes in these two organisms.
2011-02-08 | E-MTAB-550 | biostudies-arrayexpress
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.
2023-01-24 | GSE217220 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE11437: Expression QTL mapping of Toxoplasma gondii genes, Bradyzoite array GSE11514: Expression QTL mapping of Toxoplasma gondii genes, Tachyzoite array Keywords: SuperSeries Refer to individual Series
2008-05-22 | E-GEOD-11515 | biostudies-arrayexpress