{"gene":"TG_300200","gene_symbol":"","run_date":"2026-09-08T15:15:12","timeline":{"discoveries":[{"year":2009,"finding":"Toxoplasma gondii H2AZ is a minor H2A variant that interacts with a novel H2B variant (H2Bv) but not with H2AX, demonstrating nucleosomes of novel composition in this parasite.","method":"Co-immunoprecipitation / protein interaction assay","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/pulldown identifying binding partners, supported by ChIP data in the same study, single lab","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"finding":"Chromatin immunoprecipitation (ChIP) revealed that H2AZ (together with H2Bv) is enriched at transcriptionally active genes, indicating a role for H2AZ in marking active chromatin in Toxoplasma.","method":"Chromatin immunoprecipitation (ChIP)","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct ChIP localization tied to functional chromatin state, single lab, single method","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"finding":"h2az transcript is expressed in mature bradyzoites (in vivo, G0-arrested) but not detected to increase during in vitro bradyzoite differentiation, distinguishing its expression pattern from h2ax and h2a1 across life-cycle stages.","method":"Transcriptional analysis across parasite life stages (tachyzoite vs. bradyzoite in vitro and in vivo)","journal":"Journal of molecular biology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — expression-based life-stage comparison with no direct functional manipulation of H2AZ","pmids":["19607843"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"In Toxoplasma gondii, histone H2AZ is a minor H2A variant that forms novel nucleosome compositions by associating with a parasite-specific H2B variant (H2Bv) but not with H2AX; ChIP evidence places H2AZ/H2Bv-containing nucleosomes at transcriptionally active genes, suggesting H2AZ marks permissive chromatin, while its expression persists in G0-arrested bradyzoites in contrast to the canonical H2A1."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, histone H2AZ is a minor H2A variant that assembles into nucleosomes of novel composition by pairing with a parasite-specific H2B variant (H2Bv) rather than with the DNA-damage-associated variant H2AX [PMID:19607843]. Chromatin immunoprecipitation places H2AZ/H2Bv-containing nucleosomes at transcriptionally active genes, marking H2AZ as a feature of permissive chromatin in this parasite [PMID:19607843]. Beyond this variant-pairing and active-gene localization, no further mechanistic detail—deposition machinery, structural basis of the atypical dimer, or direct functional consequence of H2AZ loss—has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Whether Toxoplasma H2AZ behaves like a canonical H2A variant was unknown; showing it partners with a novel H2B variant rather than H2AX established that this parasite builds nucleosomes of unusual histone composition.","evidence":"Co-immunoprecipitation / protein interaction assay in Toxoplasma gondii","pmids":["19607843"],"confidence":"Medium","gaps":["single Co-IP without reciprocal or structural validation of the H2AZ/H2Bv dimer","deposition/eviction machinery (chaperones, remodelers) not identified","no test of whether H2AZ can pair with any canonical H2B"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"claim":"It was unclear where H2AZ-containing nucleosomes reside in the genome; ChIP enrichment at transcriptionally active genes established a link between H2AZ and permissive chromatin state.","evidence":"Chromatin immunoprecipitation (ChIP) in Toxoplasma gondii","pmids":["19607843"],"confidence":"Medium","gaps":["correlation between localization and transcription does not establish a causal role in gene activation","no loss-of-function experiment to test whether H2AZ is required for active transcription","genome-wide distribution and promoter-versus-body positioning not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2009,"claim":"Whether H2AZ expression is stage-regulated across the parasite life cycle was open; detecting h2az transcript in mature G0-arrested bradyzoites distinguished its expression from h2ax and h2a1 and hinted at a role persisting outside active proliferation.","evidence":"Transcriptional analysis across tachyzoite and bradyzoite stages (in vitro and in vivo) in Toxoplasma gondii","pmids":["19607843"],"confidence":"Low","gaps":["expression-only comparison with no functional manipulation of H2AZ","protein-level and chromatin-incorporation data in bradyzoites not shown","functional significance of persistent expression in G0-arrested cells unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The deposition machinery, structural basis of the H2AZ/H2Bv nucleosome, and the causal requirement of H2AZ for active transcription or bradyzoite biology remain uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["no chaperone or remodeler linked to H2AZ deposition","no loss-of-function phenotype established","no structural characterization of the atypical H2AZ/H2Bv dimer"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["H2AZ/H2Bv-containing nucleosome (novel composition)"],"partners":["H2BV (PARASITE-SPECIFIC H2B VARIANT)"],"other_free_text":["Does not interact with H2AX [#0]","Enriched at transcriptionally active genes by ChIP [#1]","h2az transcript detected in mature G0-arrested bradyzoites in vivo, unlike h2ax and h2a1 [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"19607843","id":"PMC_19607843","title":"Toxoplasma H2A variants reveal novel insights into nucleosome composition and functions for this histone family.","date":"2009","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19607843","citation_count":51,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3071,"output_tokens":761,"usd":0.010314,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5555,"output_tokens":1953,"usd":0.0383,"stage2_stop_reason":"end_turn"},"total_usd":0.048614,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"Toxoplasma gondii H2AZ is a minor H2A variant that interacts with a novel H2B variant (H2Bv) but not with H2AX, demonstrating nucleosomes of novel composition in this parasite.\",\n      \"method\": \"Co-immunoprecipitation / protein interaction assay\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/pulldown identifying binding partners, supported by ChIP data in the same study, single lab\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Chromatin immunoprecipitation (ChIP) revealed that H2AZ (together with H2Bv) is enriched at transcriptionally active genes, indicating a role for H2AZ in marking active chromatin in Toxoplasma.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct ChIP localization tied to functional chromatin state, single lab, single method\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"h2az transcript is expressed in mature bradyzoites (in vivo, G0-arrested) but not detected to increase during in vitro bradyzoite differentiation, distinguishing its expression pattern from h2ax and h2a1 across life-cycle stages.\",\n      \"method\": \"Transcriptional analysis across parasite life stages (tachyzoite vs. bradyzoite in vitro and in vivo)\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — expression-based life-stage comparison with no direct functional manipulation of H2AZ\",\n      \"pmids\": [\"19607843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In Toxoplasma gondii, histone H2AZ is a minor H2A variant that forms novel nucleosome compositions by associating with a parasite-specific H2B variant (H2Bv) but not with H2AX; ChIP evidence places H2AZ/H2Bv-containing nucleosomes at transcriptionally active genes, suggesting H2AZ marks permissive chromatin, while its expression persists in G0-arrested bradyzoites in contrast to the canonical H2A1.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, histone H2AZ is a minor H2A variant that assembles into nucleosomes of novel composition by pairing with a parasite-specific H2B variant (H2Bv) rather than with the DNA-damage-associated variant H2AX [#0]. Chromatin immunoprecipitation places H2AZ/H2Bv-containing nucleosomes at transcriptionally active genes, marking H2AZ as a feature of permissive chromatin in this parasite [#1]. Beyond this variant-pairing and active-gene localization, no further mechanistic detail—deposition machinery, structural basis of the atypical dimer, or direct functional consequence of H2AZ loss—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether Toxoplasma H2AZ behaves like a canonical H2A variant was unknown; showing it partners with a novel H2B variant rather than H2AX established that this parasite builds nucleosomes of unusual histone composition.\",\n      \"evidence\": \"Co-immunoprecipitation / protein interaction assay in Toxoplasma gondii\",\n      \"pmids\": [\"19607843\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"single Co-IP/pulldown identifying binding partners, single lab\",\n      \"gaps\": [\n        \"single Co-IP without reciprocal or structural validation of the H2AZ/H2Bv dimer\",\n        \"deposition/eviction machinery (chaperones, remodelers) not identified\",\n        \"no test of whether H2AZ can pair with any canonical H2B\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"It was unclear where H2AZ-containing nucleosomes reside in the genome; ChIP enrichment at transcriptionally active genes established a link between H2AZ and permissive chromatin state.\",\n      \"evidence\": \"Chromatin immunoprecipitation (ChIP) in Toxoplasma gondii\",\n      \"pmids\": [\"19607843\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"direct ChIP localization tied to functional chromatin state, single lab, single method\",\n      \"gaps\": [\n        \"correlation between localization and transcription does not establish a causal role in gene activation\",\n        \"no loss-of-function experiment to test whether H2AZ is required for active transcription\",\n        \"genome-wide distribution and promoter-versus-body positioning not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether H2AZ expression is stage-regulated across the parasite life cycle was open; detecting h2az transcript in mature G0-arrested bradyzoites distinguished its expression from h2ax and h2a1 and hinted at a role persisting outside active proliferation.\",\n      \"evidence\": \"Transcriptional analysis across tachyzoite and bradyzoite stages (in vitro and in vivo) in Toxoplasma gondii\",\n      \"pmids\": [\"19607843\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"expression-based life-stage comparison with no direct functional manipulation\",\n      \"gaps\": [\n        \"expression-only comparison with no functional manipulation of H2AZ\",\n        \"protein-level and chromatin-incorporation data in bradyzoites not shown\",\n        \"functional significance of persistent expression in G0-arrested cells unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The deposition machinery, structural basis of the H2AZ/H2Bv nucleosome, and the causal requirement of H2AZ for active transcription or bradyzoite biology remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no chaperone or remodeler linked to H2AZ deposition\",\n        \"no loss-of-function phenotype established\",\n        \"no structural characterization of the atypical H2AZ/H2Bv dimer\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0030527\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000786\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"H2AZ/H2Bv-containing nucleosome (novel composition)\"\n    ],\n    \"partners\": [\n      \"H2Bv (parasite-specific H2B variant)\"\n    ],\n    \"other_free_text\": [\n      \"Does not interact with H2AX [#0]\",\n      \"Enriched at transcriptionally active genes by ChIP [#1]\",\n      \"h2az transcript detected in mature G0-arrested bradyzoites in vivo, unlike h2ax and h2a1 [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_300200","name":null,"product":"histone H2AZ","uniprot_acc":"A0A125YP81","chromosome":"TGME49_chrXII","start_pos":160424},{"strain":"GT1","gene_id":"TGGT1_300200","name":null,"product":"histone H2AZ","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":122117},{"strain":"RH88","gene_id":"TGRH88_057170","name":null,"product":"histone H2AZ","uniprot_acc":null,"chromosome":"CM023093","start_pos":151493},{"strain":"VEG","gene_id":"TGVEG_300200","name":null,"product":"histone H2AZ","uniprot_acc":"A0A0F7V6C1","chromosome":"TGVEG_chrXII","start_pos":151840}]}