ArticleProceedings of the National Academy of Sciences of the United States of America2013
ApiAP2 transcription factor restricts development of the Toxoplasma tissue cyst.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 143 citations in OpenAlex.
- A Live Attenuated AP2X-1-DeficientAnimals : an open access journal from MDPI · 2026Article
- Protein arginine methyltransferase 5 is essential for virulence in Toxoplasma gondii.Parasites & vectors · 2026Article
- Host-cell dependent epigenetic profiles associated with survival outcomes in T. gondii infection.Epigenetics & chromatin · 2026Article
- A single-cell atlas of Toxoplasma sexual development in the feline intestinal tract.Nature microbiology · 2026Article
- A single-cell atlas ofbioRxiv : the preprint server for biology · 2026Article
- AP2X-1 is a negative regulator ofmBio · 2025Article
- Regulation of the developmental programs in Toxoplasma by a novel SNF2L-containing chromatin remodeling complex.Nature communications · 2025Article
- AP2X-8 Is Important for Tachyzoite Growth and Bradyzoite Differentiation ofAnimals : an open access journal from MDPI · 2025Article
- Molecular mechanisms of surface antigen suppression by ApiAP2 and its implications for vaccine development.Veterinary research · 2025Article
- A Novel Nuclear Protein Complex Controlling the Expression of Developmentally Regulated Genes in Toxoplasma Gondii.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cascading expression of ApiAP2 transcription factors controls daughter cell assembly in Toxoplasma gondii.PLoS pathogens · 2024Article
- Article
- Functional Characterization of Six Eukaryotic Translation Initiation Factors ofInternational journal of molecular sciences · 2024Article
- Article
- The Crk4-Cyc4 complex regulates GThe EMBO journal · 2024Article
- AP2XII-1 and AP2XI-2 Suppress Schizogony Gene Expression inInternational journal of molecular sciences · 2024Article
- Cryptosporidium life cycle small molecule probing implicates translational repression and an Apetala 2 transcription factor in macrogamont differentiation.PLoS pathogens · 2024Article
- Sex in a dish: high-efficiency Toxoplasma pre-sexual development.Trends in parasitology · 2024Article
- Constitutive upregulation of transcription factors underlies permissive bradyzoite differentiation in a natural isolate ofbioRxiv : the preprint server for biology · 2024Article
- The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony.Nature communications · 2024Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
Cellular differentiation leading to formation of the bradyzoite tissue cyst stage is the underlying cause of chronic toxoplasmosis. Consequently, mechanisms responsible for controlling development in the Toxoplasma intermediate life cycle have long been sought. Here, we identified 15 Toxoplasma mRNAs induced in early bradyzoite development that encode proteins with apicomplexan AP2 (ApiAP2) DNA binding domains. Of these 15 mRNAs, the AP2IX-9 mRNA demonstrated the largest expression increase during alkaline-induced differentiation. At the protein level, we found that AP2IX-9 was restricted to the early bradyzoite nucleus and is repressed in tachyzoites and in mature bradyzoites from 30-d infected animals. Conditional overexpression of AP2IX-9 significantly reduced tissue cyst formation and conferred alkaline pH-resistant growth, whereas disruption of the AP2IX-9 gene increased tissue cyst formation, indicating AP2IX-9 operates as a repressor of bradyzoite development. Consistent with a role as a repressor, AP2IX-9 specifically inhibited the expression of bradyzoite mRNAs, including the canonical bradyzoite marker, bradyzoite antigen 1 (BAG1). Using protein binding microarrays, we established the AP2 domain of AP2IX-9 binds a CAGTGT DNA sequence motif and is capable of binding cis-regulatory elements controlling the BAG1 and bradyzoite-specific nucleoside triphosphatase (B-NTPase) promoters. The effect of AP2IX-9 on BAG1 expression was direct because this factor inhibits expression of a firefly luciferase reporter under the control of the BAG1 promoter in vivo, and epitope-tagged AP2IX-9 can be immunoprecipitated with the BAG1 promoter in parasite chromatin. Altogether, these results indicate AP2IX-9 restricts Toxoplasma commitment to develop the mature bradyzoite tissue cyst.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.