Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Toxoplasma gondii transcription factor AP2XII-8 is a key regulator for the G1 phase progression and parasite division

ABSTRACT: The apicomplexan parasite Toxoplasma gondii can infect humans and almost all warm-blooded animals worldwide, poses significant threat to the public health and of veterinary importance. The acute infection was characterized by fast replication of tachyzoites inside the host cells. During this fast amplification process, the gene expression is highly regulated by series of regulator networks. The G1 phase is usually conserved across species and responsible for the preparation of materials for the next replication cell cycle, but seldom regulators were identified in this stage. Here, we functionally characterized the C/G1 phase expressed ApiAP2 transcription factor TgAP2XII-8 in T. gondii tachyzoite. Conditionally knockdown of TgAP2XII-8 leads to significant growth defects and asexual division disorder. Additionally, the parasite cell cycle progression was also disrupted after TgAP2XII-8 depletion, which is characterized by G1 phase arrest. RNA-seq and CUT&Tag experiments revealed that TgAP2XII-8 played as an activator for the ribosomal proteins expressed in G1 phase. Moreover, TgAP2XII-8 bind to a specific DNA motif ([T/C]GCATGCA), which is abundant and conserved in the intergenic region of several other apicomplexans, which may suggest a broad and conserved role for this ApiAP2 in the Phylum of Apicomplexa. These data provide important knowledge for the understanding of transcriptional regulation of parasite cell cycle in T. gondii.

ORGANISM(S): Toxoplasma gondii

PROVIDER: GSE275112 | GEO | 2024/08/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cyclical transcription factor AP2XII-9 is a key activator for asexual division and apicoplast inheritance in Toxoplasma gondii tachyzoite

Project description:Toxoplasma gondii is an intracellular parasitic protozoan that poses a significant risk to pregnant women and immunocompromised individuals. T. gondii tachyzoites duplicate rapidly in host cells during acute infection through endodyogeny. This highly regulated division process is accompanied by complex gene regulation networks. TgAP2XII-9 is a cyclical transcription factor, but its specific role in the parasite cell cycle is not fully understood. Here, we demonstrate that TgAP2XII-9 is identified as a nuclear transcription factor and is dominantly expressed during the S/M phase of the tachyzoite cell cycle. CUT&Tag results indicate that TgAP2XII-9 targets key genes for the moving junction machinery (RON2, 4, 8) and daughter cell inner membrane complex (IMC). TgAP2XII-9 deficiency resulted in a significant downregulation of rhoptry proteins and rhoptry neck proteins, leading to a severe defect in the invasion and egress efficiency of tachyzoites. Additionally, the loss of TgAP2XII-9 correlated with a substantial downregulation of multiple IMC and apicoplast proteins, leading to disorders of daughter bud formation and apicoplast inheritance, and further contributing to the inability of cell division and intracellular proliferation. Our study reveals that TgAP2XII-9 acts as a critical S/M-phase regulator that orchestrates the endodyogeny and apicoplast division in T. gondii tachyzoite. This study contributes to a broader understanding of the complexity of the parasite’s cell cycle and its key regulators.

2024-05-05 | GSE266204 | GEO

Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii. [RNA-seq]

Project description:Toxoplasma gondii is a unicellular eukaryote belonging to the Apicomplexa phylum. It is an obligate intracellular parasite of critical importance to primarily infected pregnant women and immunosuppressed patient. ApiAP2 are a family of conserved transcription factors (TF) that play an important role in regulating gene expression in apicomplexan parasites. Previous studies had revealed the ability of one of these TFs, TgAP2XI-5, to bind to transcriptionally active promoters of genes expressed during the S/M phase such as rhoptry and micronemes genes. However, expression of TgAP2XI-5 is constitutive during the tachyzoite cell cycle. To better understand how its function is regulated, we identified proteins interacting with TgAP2XI-5 including a cell cycle regulated ApiAP2 TFs, TgAP2X-5. The purpose of the study is to determine the impact of the absence of a TF (TgAP2X-5) on the wide expression profile of a Toxoplasma gondii strain.

2018-05-30 | GSE106864 | GEO

Coordinated Progression Through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

2010-08-27 | GSE19092 | GEO

Coordinated Progression Through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

Project description:We describe the cell cycle transcriptome of the Toxoplasma gondii that has emerged as a major genetic model for the study of Apicomplexa parasites. Two distinct transcriptional waves accompany the relatively simple binary replication of tachyzoite stage (endodyogeny) functionally separating conserved gene expression in the eukaryotic G1 phase from the lineage-specific expression that predominates in the parasite S phase and mitotic periods. This division of transcriptional focus closely mirrors the intimate relationship that has evolved between mitosis and building of the daughter parasites and invasion organelles. Promoter mechanisms appear to orchestrate the induction of gene expression in dividing tachyzoites with up to two dozen cell cycle AP2 factors likely acting within a transcriptional regulatory network to coordinate the parasite cell cycle transcriptome. To characterize the cell cycle transcriptome of Toxoplasma tachyzoites, we expanded a thymidine-synchrony model to isolate sufficient RNA for microarray expression studies. The ToxoGeneChip microarray (http://ancillary.toxodb.org/docs/Array-Tutorial.html) was used to measure mRNA expression in 13 duplicate samples (R0 to R12) covering 12 hours post-synchronization and nearly two tachyzoite replication cycles.

2010-08-27 | E-GEOD-19092 | biostudies-arrayexpress

A nucleolar AAA-NTPase is required for Toxoplasma gondii division

2013-01-27 | GSE43784 | GEO

Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii. [ChIP-chip]

Project description:Toxoplasma gondii is a unicellular eukaryote belonging to the Apicomplexa phylum. It is an obligate intracellular parasite of critical importance to primarily infected pregnant women and immunosuppressed patient. ApiAP2 are a family of conserved transcription factors (TF) that play an important role in regulating gene expression in apicomplexan parasites. Previous studies had revealed the ability of one of these TFs, TgAP2XI-5, to bind to transcriptionally active promoters of genes expressed during the S/M phase such as rhoptry and micronemes genes. However, expression of TgAP2XI-5 is constitutive during the tachyzoite cell cycle. To better understand how its function is regulated, we identified proteins interacting with TgAP2XI-5 including a cell cycle regulated ApiAP2 TFs, TgAP2X-5. The purpose of the study is to determine the impact of the absence of TgAP2X-5 on the binding of TgAP2XI-5 on its targets. Chromatin immunoprecipitation (ChIP) of TgAP2XI-5 together with chromatin in absence of TgAP2X-5 profiling by ChIP-on-chip analysis demonstrated that TgAP2X-5 co-acts with TgAP2XI-5 for its binding to DNA of certain promoter targets.

2018-05-30 | GSE109086 | GEO

A nucleolar AAA-NTPase is required for Toxoplasma gondii division

Project description:Toxoplasma gondii cell cycle mutant 11-104A4 reversibly arrests in the G1 phase. The defect in this mutant was mapped by genetic complementation to a gene encoding a novel AAA-ATPase/CDC48 family member (TgNoAP1). A change in a tyrosine to a cysteine upstream of an AAA+ domain leads to protein instability and results in cell cycle arrest. This factor is cell cycle regulated and exclusively expressed in the nucleolus during the G1/S phases. At high temperature the mutant quickly arrests with a single nucleus and expresses transcripts enriched in the G1 subtranscriptome. This unique CDC48 ortholog operates in a parasite mechanism responsible for G1 progression and is the first G1-specific checkpoint factor described in Toxoplasma. We describe transcriptome of the temperature sensitive mutant 11-104A4. Transcriptome studies demonstrated that gene expression is reflective of the parasite arrest in G1 phase. mRNAs normally upregulated in S/M phase were largely downregulated in the mutant at the restrictive temperature 40oC. Genetic complementation with extra copy of the wild type TgNoAP1 rescued growth of the mutant 11-104A4 at 40oC and reversed changes in the transcriptome. RNA samples were isolated in duplicate from mutant 11-104A4 parasites grown for 32h at permissive (34oC) or non-permissive temperatures (40oC). In addition, a duplicate sample of RNA from mutant 11-104A4 complemented with cosmid TOXOV53 encoding wild type copy of TgNoAP1 similarly grown at 40oC was collected. Samples were hybridized to the Toxoplasma gondii Affymetrix microarray (ToxoGeneChip: http://ancillary.toxodb.org/docs/Array-Tutorial.html). Hybridization data was preprocessed with Robust Multi-array Average (RMA) and normalized using per chip and per gene median polishing and analyzed using the software package GeneSpring GX (Agilent Technologies).

2013-01-27 | E-GEOD-43784 | biostudies-arrayexpress

Genome-wide mapping of nucleosome positioning in Toxoplasma gondii implicates nucleosome-free regions as the major gene regulatory regions

Project description:Nucleosome organization is critical for the regulation of gene expression, and genome-scale mapping of nucleosomes has revealed a conserved, highly ordered pattern in nucleosome positioning. Most genome-wide studies have been performed in model organisms and little is known about nucleosome positioning in evolutionarily divergent eukaryotes. We generated a high-resolution nucleosome map of the protozoan parasite Toxoplasma gondii from four high quality MNase-Seq datasets. T. gondii nucleosomes are organised in phase around the transcription start sites (TSSs) with a canonical pattern that is conserved across eukaryotes. Nucleosome occupancy in exons is influenced by several factors, including GC content, length of exons and strength of splice sites. Poly(dA:dT) is enriched at the +1 nucleosome rather than nucleosome-free regions (NFRs) and serves as the key sequence associated with nucleosome formation in T. gondii. Motif analysis of sequences in NFR1, adjacent to the transcription start site, revealed enrichment of DNA-binding motifs recognized by members of the plant-like ApiAP2 transcription factor family that is conserved across Apicomplexa. Genes associated with the two most common motifs are enriched in genes upregulated during two major waves of mRNA accumulation within the cell cycle. Genome-wide peaks from T. gondii assays for transposase-accessible chromatin using sequencing (ATAC-seq) coincide with NFR1, consistent with the enrichment of T. gondii open chromatin regulatory regions localizing to close to transcription initiation sites. Finally, by integrating the map of nucleosome positions with ChIP-seq we suggest that nucleosome positioning and placement of histone variants and histone modifications play roles in splicing of genes in T. gondii.

2017-09-08 | GSE86620 | GEO

Cell cycle-dependent, intercellular transmission of Toxoplasma gondii is accompanied by marked changes in parasite gene expression.

Project description:Intracellular microbes have evolved efficient strategies for transitioning from one cell to another in a process termed intercellular transmission. Here we show that host cell transmission of the obligate intracellular parasite Toxoplasma gondii is closely tied to specific cell cycle distributions, with egress and reinvasion occurring most proficiently by parasites in the G1 phase. We also reveal that Toxoplasma undergoes marked changes in mRNA expression when transitioning from the extracellular environment to its intracellular niche. These mRNA level changes reflect a modal switch from expression of proteins involved in invasion, motility and signal transduction in extracellular parasites to expression of metabolic and DNA replication proteins in intracellular parasites. Host cell binding and signalling associated with the discharge of parasite secretory proteins was not sufficient to induce this switch in gene expression, suggesting that the regulatory mechanisms responsible are tied to the establishment of the intracellular environment. The genes whose expression increased after parasite invasion belong to a progressive cascade known to underlie the parasite division cycle indicating that the unique relationship between the G1 phase and invasion effectively synchronizes short-term population growth. This work provides new insight into how this highly successful parasite competently transits from cell to cell. Three sample types were harvested: extracellular, intracellular 0hr, intracellular 2hr. 2 replicates each. Expression for >80% of the regulated genes exhibits a steady downregulation during invasion.

2010-12-27 | E-GEOD-20480 | biostudies-arrayexpress

Cell cycle-dependent, intercellular transmission of Toxoplasma gondii is accompanied by marked changes in parasite gene expression.

2010-12-27 | GSE20480 | GEO