To identify HDAC3 occupancy in the genomes of ME49 and ΔXII-5 strains
Ontology highlight
ABSTRACT:
ORGANISM(S): Toxoplasma gondii
PROVIDER: GSE283441 | GEO | 2024/12/19
REPOSITORIES: GEO
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: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:Background: Considerable work has been carried out to understand the biology of the intermediate stages, the tachyzoite and bradyzoite, of Toxoplasma gondii in large part due to the accessible culturing methods for these stages. However, culturing methods for stages beyond the bradyzoite, including the merozoite and sexual stages, have not been developed hindering the ability to study a large portion of the parasite’s life cycle. We begin to unravel the molecular aspects of the merozoite stage focusing on gene expression. Results: To initiate this, we harvested merozoite parasites and hybridized mRNA to the Affymetrix Toxoplasma GeneChip. We analyzed the merozoite data in context of the life cycle by combining it with a previously published study that generated array data for the oocyst, tachyzoite, and bradyzoite stages (Fritz HM et al. PLoS One, 2012). Principal component analysis highlights the unique profile of the merozoite samples, placing them approximately half-way on a continuum between the tachyzoite/bradyzoite and oocyst samples. Prior studies have shown that antibodies to surface antigen p30 (SAG1) and many dense granule proteins do not label merozoites, and our microarray data confirms that these genes are not expressed at this stage. Also, the expression for many rhoptry and microneme proteins is drastically reduced while the expression for many surface antigens is increased at the merozoite stage. Gene Ontology and KEGG analysis reveals that genes involved in transcription/translation and many metabolic pathways are upregulated at the merozoite stage, highlighting unique growth requirements of this stage. We also show that an upstream promoter region of a merozoite specific gene is sufficient to control stage specific expression at the merozoite stage. Conclusion: The merozoite represents the first developmental stage within the gut of the definitive host. Determining the correct conditions that coax the parasite into the merozoite stage in vitro may allow the parasite to complete sexual development. The data presented here describe the global gene expression profile of merozoite stage and the creation of transgenic parasite strains that will be useful in unlocking how the parasite senses and responds to the felid gut environment to initiate coccidian development. The ToxoGeneChip microarray was used to measure both tachyzoite and merozoite mRNA expression in the type II TgNmBr1 strain.
2014-05-02 | E-GEOD-51780 | biostudies-arrayexpress
Project description:Toxoplasma gondii is a medically and veterinary important intracellular parasite that 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 ApiApiAP2 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 three primary ApiAP2s: ApiAP2XII-1, ApiAP2XI-2, and ApiAP2V-2, demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of ApiAP2XII-1 and ApiAP2XI-2 resulted in a more profound alteration in merozoite-specific genes targeted by the MORC/HDAC3 complex compared to ApiAP2V-2. Additionally, considerable overlap was observed in downstream gene profiles between ApiAP2XII-1 and ApiAP2XI-2, with ApiAP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including ApiAP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by ApiAP2XII-1 and ApiAP2XI-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.
2023-12-10 | GSE249604 | GEO
Project description:Background: Considerable work has been carried out to understand the biology of the intermediate stages, the tachyzoite and bradyzoite, of Toxoplasma gondii in large part due to the accessible culturing methods for these stages. However, culturing methods for stages beyond the bradyzoite, including the merozoite and sexual stages, have not been developed hindering the ability to study a large portion of the parasite’s life cycle. We begin to unravel the molecular aspects of the merozoite stage focusing on gene expression. Results: To initiate this, we harvested merozoite parasites and hybridized mRNA to the Affymetrix Toxoplasma GeneChip. We analyzed the merozoite data in context of the life cycle by combining it with a previously published study that generated array data for the oocyst, tachyzoite, and bradyzoite stages (Fritz HM et al. PLoS One, 2012). Principal component analysis highlights the unique profile of the merozoite samples, placing them approximately half-way on a continuum between the tachyzoite/bradyzoite and oocyst samples. Prior studies have shown that antibodies to surface antigen p30 (SAG1) and many dense granule proteins do not label merozoites, and our microarray data confirms that these genes are not expressed at this stage. Also, the expression for many rhoptry and microneme proteins is drastically reduced while the expression for many surface antigens is increased at the merozoite stage. Gene Ontology and KEGG analysis reveals that genes involved in transcription/translation and many metabolic pathways are upregulated at the merozoite stage, highlighting unique growth requirements of this stage. We also show that an upstream promoter region of a merozoite specific gene is sufficient to control stage specific expression at the merozoite stage. Conclusion: The merozoite represents the first developmental stage within the gut of the definitive host. Determining the correct conditions that coax the parasite into the merozoite stage in vitro may allow the parasite to complete sexual development. The data presented here describe the global gene expression profile of merozoite stage and the creation of transgenic parasite strains that will be useful in unlocking how the parasite senses and responds to the felid gut environment to initiate coccidian development.
2014-05-02 | GSE51780 | GEO
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: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 | GSE217226 | GEO
Project description:Asexual development in Toxoplasma gondii is a vital aspect of the parasite's life cycle, allowing transmission and avoidance of the host immune response. Differentiation of rapidly dividing tachyzoites into slowly growing, encysted bradyzoites involves significant changes in both physiology and morphology. We generated microarrays of 4,400 Toxoplasma cDNAs, representing a minimum of 600 genes (based on partial sequencing), and used these microarrays to study changes in transcript levels during tachyzoite-to-bradyzoite differentiation. This approach has allowed us to (i) determine expression profiles of previously described developmentally regulated genes, (ii) identify novel developmentally regulated genes, and (iii) identify distinct classes of genes based on the timing and magnitude of changes in transcript levels. Whereas microarray analysis typically involves comparisons of mRNA levels at different time points, we have developed a method to measure relative transcript abundance between genes at a given time point. This method was used to determine transcript levels in parasites prior to differentiation and to further classify bradyzoite-induced genes, thus allowing a more comprehensive view of changes in gene expression than is provided by standard expression profiles. Newly identified developmentally regulated genes include putative surface proteins (a SAG1-related protein, SRS9, and a mucin-domain containing protein), regulatory and metabolic enzymes (methionine aminopeptidase, oligopeptidase, aminotransferase, and glucose- 6-phosphate dehydrogenase homologues), and a subset of genes encoding secretory organelle proteins (MIC1, ROP1, ROP2, ROP4, GRA1, GRA5, and GRA8). This analysis permits the first in depth look at changes in gene expression during development of this complex protozoan parasite.
2005-07-21 | E-SMDB-1428 | biostudies-arrayexpress
Project description:Plasmodium and Toxoplasma are parasites of major medical importance that belong to the Apicomplexa phylum of protozoa. These parasites transform into various stages during their life cycle and express a specific set of proteins at each stage. Although still little is known of how gene expression is controlled in Apicomplexa, histone modifications, particularly acetylation, are emerging as key regulators of parasite differentiation and stage conversion. Here, we investigated the anti-Apicomplexa effect of FR235222, a histone deacetylase (HDAC) inhibitor. We show that FR235222 is active against a variety of Apicomplexa genera, including Plasmodium and Toxoplasma, and is more potent than other HDACi such as TSA and the clinically relevant compound, pyrimethamine. We identify TgHDAC3 as the target of FR235222 in Toxoplasma tachyzoites and demonstrate the crucial role of the conserved and Apicomplexa HDAC-specific residue TgHDAC3 T99 in the inhibitory activity of the drug. We also show that FR235222 induces differentiation of the tachyzoite (replicative) into the bradyzoite (non replicative) stage. Additionally, via its anti-TgHDAC3 activity, FR235222 influences the expression of ~370 genes, a third of which are stage-specifically expressed. These results identify FR235222 as a potent HDAC inhibitor of Apicomplexa, and establish HDAC3 as a central regulator of gene expression and stage conversion in Toxoplasma and likely other Apicomplexa.
2009-03-19 | GSE15241 | GEO
Project description:Developmental switching in Toxoplasma gondii, from the virulent tachyzoite to the relatively quiescent bradyzoite stage, is responsible for disease propagation and reactivation. We have generated tachyzoite to bradyzoite differentiation (Tbd-) mutants in T. gondii and used these in combination with a cDNA microarray to identify developmental pathways in bradyzoite formation. Four independently generated Tbd- mutants were analysed and had defects in bradyzoite development in response to multiple bradyzoite-inducing conditions, a stable phenotype after in vivo passages and a markedly reduced brain cyst burden in a murine model of chronic infection. Transcriptional profiles of mutant and wild-type parasites, growing under bradyzoite conditions, revealed a hierarchy of developmentally regulated genes, including many bradyzoite-induced genes whose transcripts were reduced in all mutants. A set of non-developmentally regulated genes whose transcripts were less abundant in Tbd- mutants were also identified. These may represent genes that mediate downstream effects and/or whose expression is dependent on the same transcription factors as the bradyzoite-induced set. Using these data, we have generated a model of transcription regulation during bradyzoite development in T. gondii. Our approach shows the utility of this system as a model to study developmental biology in single-celled eukaryotes including protozoa and fungi.
2005-07-21 | E-SMDB-1404 | biostudies-arrayexpress