{"gene":"TG_233120","gene_symbol":"AP2VIII2","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2025,"finding":"AP2VIII-2 forms a core complex with the ISWI-family chromatin remodeller TgSNF2h and the scaffold protein TgRFTS in Toxoplasma gondii. Depletion of TgRFTS phenocopies TgSNF2h knockdown, restricting chromatin access and altering local gene expression. At the genomic level, TgSNF2h (with AP2VIII-2 as a partner) insulates highly transcribed genes from silenced neighbours and exerts epistatic control over MORC, a key regulator of sexual commitment.","method":"Co-immunoprecipitation / proteomics to identify the complex; conditional knockdown with phenotypic readout (chromatin accessibility, gene expression); epistasis analysis relative to MORC","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification, conditional knockdown phenocopying, epistasis with MORC, and chromatin accessibility assays in a single rigorous peer-reviewed study","pmids":["40217127"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AP2VIII-2 is a transcription factor that physically associates with the ISWI-family chromatin remodeller TgSNF2h and the scaffold protein TgRFTS to form a core complex that modulates chromatin accessibility, insulates highly transcribed genes from silenced neighbours, and exerts epistatic control over the sexual-commitment regulator MORC, thereby contributing to stage-specific gene regulation in Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"AP2VIII-2 is a transcription-factor component of a chromatin-regulatory complex that shapes stage-specific gene expression in Toxoplasma gondii [PMID:40217127]. It physically associates with the ISWI-family chromatin remodeller TgSNF2h and the scaffold protein TgRFTS to form a core complex; within this complex TgSNF2h insulates highly transcribed genes from silenced neighbours and exerts epistatic control over MORC, a key regulator of sexual commitment [PMID:40217127]. Depletion of TgRFTS phenocopies TgSNF2h knockdown by restricting chromatin access and altering local gene expression [PMID:40217127]. Beyond this single complex-level characterization, no further mechanistic detail — including AP2VIII-2's direct DNA-binding targets or its individual contribution separable from TgSNF2h — has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"The question of how a specific ApiAP2 transcription factor connects to chromatin remodelling was answered by placing AP2VIII-2 in a defined complex with TgSNF2h and TgRFTS that controls chromatin accessibility and stage-specific gene regulation.","evidence":"Co-immunoprecipitation/proteomics to define the complex, conditional knockdown with chromatin accessibility and gene-expression readouts, and epistasis analysis relative to MORC in Toxoplasma gondii","pmids":["40217127"],"confidence":"High","gaps":["The direct DNA-binding sites and target genes of AP2VIII-2 itself are not resolved","The specific contribution of AP2VIII-2 loss (versus TgSNF2h or TgRFTS depletion) to the observed phenotypes is not separated","The structural organization and stoichiometry of the AP2VIII-2/TgSNF2h/TgRFTS complex are undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether AP2VIII-2 directs sequence-specific targeting of the remodelling complex to insulated loci and how it governs MORC-dependent sexual commitment remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No genome-wide occupancy map for AP2VIII-2 has been established","The mechanism by which the complex insulates transcribed genes from silenced neighbours is not defined at the molecular level"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["AP2VIII-2 / TgSNF2h / TgRFTS core chromatin-remodelling complex"],"partners":["TGSNF2H (ISWI-FAMILY CHROMATIN REMODELLER)","TGRFTS (SCAFFOLD PROTEIN)","MORC (EPISTATIC TARGET; REGULATOR OF SEXUAL COMMITMENT)"],"other_free_text":["Depletion of TgRFTS phenocopies TgSNF2h knockdown, restricting chromatin access and altering local gene expression [#0]","The complex insulates highly transcribed genes from silenced neighbours and exerts epistatic control over MORC [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"20865045","id":"PMC_20865045","title":"Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/20865045","citation_count":234,"is_preprint":false},{"pmid":"29932347","id":"PMC_29932347","title":"The Epigenome, Cell Cycle, and Development in Toxoplasma.","date":"2018","source":"Annual review of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29932347","citation_count":51,"is_preprint":false},{"pmid":"20657661","id":"PMC_20657661","title":"The construction and use of log-odds substitution scores for multiple sequence alignment.","date":"2010","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/20657661","citation_count":48,"is_preprint":false},{"pmid":"19146987","id":"PMC_19146987","title":"Repeated secondary loss of adaptin complex genes in the Apicomplexa.","date":"2008","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/19146987","citation_count":36,"is_preprint":false},{"pmid":"22486860","id":"PMC_22486860","title":"Cactin is essential for G1 progression in Toxoplasma gondii.","date":"2012","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22486860","citation_count":23,"is_preprint":false},{"pmid":"25393307","id":"PMC_25393307","title":"Distinct strains of Toxoplasma gondii feature divergent transcriptomes regardless of developmental stage.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25393307","citation_count":22,"is_preprint":false},{"pmid":"18983845","id":"PMC_18983845","title":"New eukaryotic systematics: a phylogenetic perspective of developmental gene expression in the Apicomplexa.","date":"2008","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/18983845","citation_count":12,"is_preprint":false},{"pmid":"39690155","id":"PMC_39690155","title":"Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39690155","citation_count":9,"is_preprint":false},{"pmid":"40217127","id":"PMC_40217127","title":"An ISWI-related chromatin remodeller regulates stage-specific gene expression in Toxoplasma gondii.","date":"2025","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/40217127","citation_count":7,"is_preprint":false},{"pmid":"36178892","id":"PMC_36178892","title":"Genomic insights into host and parasite interactions during intracellular infection by Toxoplasma gondii.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36178892","citation_count":2,"is_preprint":false},{"pmid":"40934260","id":"PMC_40934260","title":"HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and Toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/40934260","citation_count":0,"is_preprint":false},{"pmid":"42087241","id":"PMC_42087241","title":"Host-cell dependent epigenetic profiles associated with survival outcomes in T. gondii infection.","date":"2026","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/42087241","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19456,"output_tokens":457,"usd":0.032612,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5103,"output_tokens":1458,"usd":0.030982,"stage2_stop_reason":"end_turn"},"total_usd":0.063594,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"AP2VIII-2 forms a core complex with the ISWI-family chromatin remodeller TgSNF2h and the scaffold protein TgRFTS in Toxoplasma gondii. Depletion of TgRFTS phenocopies TgSNF2h knockdown, restricting chromatin access and altering local gene expression. At the genomic level, TgSNF2h (with AP2VIII-2 as a partner) insulates highly transcribed genes from silenced neighbours and exerts epistatic control over MORC, a key regulator of sexual commitment.\",\n      \"method\": \"Co-immunoprecipitation / proteomics to identify the complex; conditional knockdown with phenotypic readout (chromatin accessibility, gene expression); epistasis analysis relative to MORC\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification, conditional knockdown phenocopying, epistasis with MORC, and chromatin accessibility assays in a single rigorous peer-reviewed study\",\n      \"pmids\": [\"40217127\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"AP2VIII-2 is a transcription factor that physically associates with the ISWI-family chromatin remodeller TgSNF2h and the scaffold protein TgRFTS to form a core complex that modulates chromatin accessibility, insulates highly transcribed genes from silenced neighbours, and exerts epistatic control over the sexual-commitment regulator MORC, thereby contributing to stage-specific gene regulation in Toxoplasma gondii.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"AP2VIII-2 is a transcription-factor component of a chromatin-regulatory complex that shapes stage-specific gene expression in Toxoplasma gondii [#0]. It physically associates with the ISWI-family chromatin remodeller TgSNF2h and the scaffold protein TgRFTS to form a core complex; within this complex TgSNF2h insulates highly transcribed genes from silenced neighbours and exerts epistatic control over MORC, a key regulator of sexual commitment [#0]. Depletion of TgRFTS phenocopies TgSNF2h knockdown by restricting chromatin access and altering local gene expression [#0]. Beyond this single complex-level characterization, no further mechanistic detail — including AP2VIII-2's direct DNA-binding targets or its individual contribution separable from TgSNF2h — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"The question of how a specific ApiAP2 transcription factor connects to chromatin remodelling was answered by placing AP2VIII-2 in a defined complex with TgSNF2h and TgRFTS that controls chromatin accessibility and stage-specific gene regulation.\",\n      \"evidence\": \"Co-immunoprecipitation/proteomics to define the complex, conditional knockdown with chromatin accessibility and gene-expression readouts, and epistasis analysis relative to MORC in Toxoplasma gondii\",\n      \"pmids\": [\"40217127\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The direct DNA-binding sites and target genes of AP2VIII-2 itself are not resolved\",\n        \"The specific contribution of AP2VIII-2 loss (versus TgSNF2h or TgRFTS depletion) to the observed phenotypes is not separated\",\n        \"The structural organization and stoichiometry of the AP2VIII-2/TgSNF2h/TgRFTS complex are undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether AP2VIII-2 directs sequence-specific targeting of the remodelling complex to insulated loci and how it governs MORC-dependent sexual commitment remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No genome-wide occupancy map for AP2VIII-2 has been established\",\n        \"The mechanism by which the complex insulates transcribed genes from silenced neighbours is not defined at the molecular level\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003700\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006338\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"AP2VIII-2 / TgSNF2h / TgRFTS core chromatin-remodelling complex\"\n    ],\n    \"partners\": [\n      \"TgSNF2h (ISWI-family chromatin remodeller)\",\n      \"TgRFTS (scaffold protein)\",\n      \"MORC (epistatic target; regulator of sexual commitment)\"\n    ],\n    \"other_free_text\": [\n      \"Depletion of TgRFTS phenocopies TgSNF2h knockdown, restricting chromatin access and altering local gene expression [#0]\",\n      \"The complex insulates highly transcribed genes from silenced neighbours and exerts epistatic control over MORC [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_233120","name":"AP2VIII2","product":"AP2 domain transcription factor AP2VIII-2","uniprot_acc":"S8GJZ9","chromosome":"TGME49_chrVIII","start_pos":2429702},{"strain":"GT1","gene_id":"TGGT1_233120","name":null,"product":"AP2 domain transcription factor AP2VIII-2","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":2426324},{"strain":"RH88","gene_id":"TGRH88_077090","name":null,"product":"AP2 domain transcription factor AP2VIII-2","uniprot_acc":null,"chromosome":"CM023089","start_pos":7536612},{"strain":"VEG","gene_id":"TGVEG_233120","name":null,"product":"AP2 domain transcription factor AP2VIII-2","uniprot_acc":"V4Z6Q7","chromosome":"TGVEG_chrVIII","start_pos":2439049}]}