Toxoplasma gondii transcription factor AP2XII-8 is a key regulator for the G1 phase progression and parasite division
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ABSTRACT:
PROVIDER: PRJNA1149468 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30290834_1.fastq.gz | Fastqsanger.gz | |||
| SRR30290834_2.fastq.gz | Fastqsanger.gz | |||
| SRR30290835_1.fastq.gz | Fastqsanger.gz | |||
| SRR30290835_2.fastq.gz | Fastqsanger.gz | |||
| SRR30290836_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2024-08-25 | GSE275112 | GEO
Project description:PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. We generated T. gondii mutants lacking PRMT1 (∆prmt1) by deletion of the PRMT1 gene. ∆prmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the complemented strain ∆prmt::PRMT1mRFP. PRMT1 localizes primarily in the cytoplasm with enrichment at the centrosome, and the strain lacking PRMT1 is unable to segregate progeny accurately. Unlike wild-type and complemented parasites, ∆prmt1 parasites have abnormal daughter buds, perturbed centrosome stoichiometry, and loss of synchronous replication. Whole genome expression profiling demonstrated differences in expression of cell cycle regulated genes in ∆prmt1 relative to the complemented ∆prmt1::PRMT1mRFP and parental wild-type strains, but these changes did not correlate with a specific block in cell cycle. Although PRMT1’s primary biological function was previously proposed to be methylation of histones, our genetic studies suggest that the most critical function of PRMT1 is within the centrosome as a regulator of daughter cell counting to assure the proper replication of the parasite. RNA samples were isolated in triplicates from RH-hxgprt parent strain (W), PRMT1 knockout (K) strain and PRMT1 knockout strain complemented with RFP-tagged PRMT1 protein (C). Parasites were grown for 32h at 37C. 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).
2015-09-18 | E-GEOD-73177 | biostudies-arrayexpress
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
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:PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. We generated T. gondii mutants lacking PRMT1 (∆prmt1) by deletion of the PRMT1 gene. ∆prmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the complemented strain ∆prmt::PRMT1mRFP. PRMT1 localizes primarily in the cytoplasm with enrichment at the centrosome, and the strain lacking PRMT1 is unable to segregate progeny accurately. Unlike wild-type and complemented parasites, ∆prmt1 parasites have abnormal daughter buds, perturbed centrosome stoichiometry, and loss of synchronous replication. Whole genome expression profiling demonstrated differences in expression of cell cycle regulated genes in ∆prmt1 relative to the complemented ∆prmt1::PRMT1mRFP and parental wild-type strains, but these changes did not correlate with a specific block in cell cycle. Although PRMT1’s primary biological function was previously proposed to be methylation of histones, our genetic studies suggest that the most critical function of PRMT1 is within the centrosome as a regulator of daughter cell counting to assure the proper replication of the parasite.
2015-09-18 | GSE73177 | GEO
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.
2013-01-27 | GSE43784 | 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:Toxoplasma gondii is an obligate intracellular protozoan parasite whose rapid lytic replication cycles define its pathogenicity. We identified a temperature sensitive growth mutant, FV-P6, which irreversibly arrests before the middle of the G1 stage of the tachyzoite cell cycle. This arrest is caused by a point mutation in a gene conserved across eukaryotes, Cactin, whose product localizes to the nucleus. To elucidate the role of TgCactin we performed genome-wide expression profiling of FV-P6 mutant parasites at 35C and 40C, as well as FV-P6 complemented with a wild-type Cactin encoding cosmid (TOXO93 or comp) and as a pseudo-diploid wild-type line encoding both the wild-type and mutant Cactin locus (S4.2), also at both temperatures. Besides the expected G1 expression profile, many genes associated with the extracellular state as well as with the bradyzoite cyst stage were identified. Consistent with these profiles were the expression of AP2 transcription factors typically associated with extracellular and bradyzoite stage parasites. This suggests a role for TgCactin in control of gene expression. Since TgCactin does not contain any functionally defined domains we reasoned TgCactin exerts its function through interactions with other proteins. In support of this model we demonstrated that TgCactin is present in a protein complex and can oligomerize. Taken together, these results suggest that TgCactin acts as a pivotal protein potentially regulating gene expression at several transition points in parasite development. The role of Cactin in G1 progression of Toxoplasma gondii tachyzoites was assessed by expression profiling a temperature senstive mutant of Cactin at both the permissive (35C) as well as the restrictive (40C) temperature. Controls under the same temperature conditions inlcude the mutant line complemented with a wild-type Cactin allele encoded on a cosmid and a wild-type parasite line expressing an additional, mutant allele of Cactin (pseudo-diploid line).
2012-03-14 | E-GEOD-36432 | biostudies-arrayexpress
Project description:Cactin is essential for G1 progression in Toxoplasma gondii
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Project description:AP2XII-2 binding sites in Toxoplasma gondii
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