{"gene":"TG_207080","gene_symbol":"MYSTB","run_date":"2026-09-08T11:06:17","timeline":{"discoveries":[{"year":2005,"finding":"TgMYST-A (a MYST family HAT paralog characterized in the same study as TgMYST-B) possesses a canonical MYST HAT catalytic domain, an atypical C2HC zinc finger, and a chromodomain; recombinant TgMYST-A acetylates histone H4 in vitro at lysines 5, 8, 12, and 16. TgMYST-B was identified as a second MYST homologue with a ~7.0-kb mRNA encoding a MYST-family lysine acetyltransferase with the same domain architecture (MYST catalytic domain, C2HC zinc finger, chromodomain).","method":"In vitro histone acetyltransferase assay with recombinant protein; bioinformatics domain analysis; mRNA transcript characterization","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay performed for TgMYST-A; TgMYST-B was identified and domain-annotated but enzymatic activity not directly assayed in this paper; single lab","pmids":["16339723"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"TgMYST-B localizes to the parasite nucleus and acetylates histones in vivo. Overexpression of catalytically active recombinant TgMYST-B reduces parasite growth rate in vitro and confers protection from a DNA-alkylating agent, whereas expression of a catalytic mutant TgMYST-B produces no growth defect and fails to protect against DNA damage, establishing that the acetyltransferase activity is required for these effects.","method":"Overexpression of wild-type and catalytic-mutant tagged TgMYST-B; in vitro growth assay; DNA-alkylating agent challenge; nuclear localization confirmed by subcellular fractionation/imaging","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — active-site mutagenesis distinguishes enzymatic from non-enzymatic effects, combined with growth and DNA-damage phenotypic readouts in a single focused study","pmids":["20159970"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"Parasites overexpressing TgMYST-B display increased levels of ATM kinase protein and phosphorylated H2AX (a DNA-damage marker), and TgMYST-B localizes to the ATM kinase gene locus, indicating TgMYST-B promotes ATM kinase expression as part of the DNA damage response. Pharmacological inhibition of ATM kinase or KATs reverses the slow-growth phenotype caused by TgMYST-B overexpression, placing TgMYST-B upstream of ATM kinase in this pathway.","method":"Immunoblot for ATM and phospho-H2AX in overexpression parasites; ChIP-localization of TgMYST-B to the ATM kinase gene; pharmacological epistasis with ATM kinase and KAT inhibitors","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (ChIP, immunoblot, pharmacological epistasis) in a single lab study","pmids":["20159970"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgMYST-B is a nuclear MYST-family lysine acetyltransferase in Toxoplasma gondii that acetylates histones, promotes ATM kinase gene expression by localizing to its locus, and thereby facilitates the ATM kinase-mediated DNA damage response; its acetyltransferase catalytic activity is required for both its growth-regulatory effect and protection against DNA-alkylating agents."},"narrative":{"mechanistic_narrative":"TgMYST-B is a nuclear MYST-family lysine acetyltransferase of Toxoplasma gondii that couples histone acetylation to the parasite DNA damage response [PMID:20159970]. It shares the MYST domain architecture of its paralog TgMYST-A — a MYST catalytic domain, an atypical C2HC zinc finger, and a chromodomain — and was identified from a ~7.0-kb mRNA [PMID:16339723]. TgMYST-B localizes to the nucleus and acetylates histones in vivo; overexpression of the catalytically active enzyme slows parasite growth and protects against a DNA-alkylating agent, while a catalytic-site mutant abolishes both effects, establishing that acetyltransferase activity is required [PMID:20159970]. Mechanistically, TgMYST-B localizes to the ATM kinase gene locus and elevates ATM kinase protein and phospho-H2AX levels, and pharmacological inhibition of either ATM kinase or KATs reverses the overexpression-induced slow growth, placing TgMYST-B upstream of ATM kinase in the DNA damage response [PMID:20159970]. Beyond this histone-acetylation-to-ATM axis, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2005,"claim":"The question of whether Toxoplasma encodes MYST-family acetyltransferases was answered by identifying two homologues, defining TgMYST-B as a MYST-family lysine acetyltransferase with a conserved catalytic-domain/zinc-finger/chromodomain architecture.","evidence":"Bioinformatic domain analysis and mRNA transcript characterization, with in vitro HAT assay on the paralog TgMYST-A acetylating histone H4","pmids":["16339723"],"confidence":"Medium","gaps":["TgMYST-B's own enzymatic activity was not directly assayed in this study","No in vivo substrate or localization established here","Histone-lysine specificity of TgMYST-B not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"claim":"Whether TgMYST-B is a functional nuclear acetyltransferase and whether its catalytic activity drives phenotypes was resolved by showing it is nuclear, acetylates histones in vivo, and that only the catalytically active form slows growth and protects against DNA alkylation.","evidence":"Overexpression of wild-type versus catalytic-mutant tagged TgMYST-B with growth assays, DNA-alkylating challenge, and subcellular localization","pmids":["20159970"],"confidence":"High","gaps":["Endogenous (non-overexpression) function not tested by knockout/knockdown","Direct histone-lysine targets in vivo not mapped","Mechanism linking acetylation to growth suppression unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"claim":"The pathway connecting TgMYST-B acetyltransferase activity to the DNA damage response was defined by placing it upstream of ATM kinase at the transcriptional level.","evidence":"Immunoblot for ATM and phospho-H2AX, ChIP-localization of TgMYST-B to the ATM kinase gene, and pharmacological epistasis with ATM kinase and KAT inhibitors in overexpression parasites","pmids":["20159970"],"confidence":"Medium","gaps":["Direct transcriptional activation of the ATM locus versus indirect effect not distinguished","Whether histone acetylation at the ATM locus is the causal event not shown","Physiological DNA-damage signal that engages TgMYST-B unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The endogenous role of TgMYST-B and its full genomic acetylation targets remain unresolved beyond overexpression phenotypes.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function (knockout/conditional) analysis in the corpus","Genome-wide acetylation targets and non-histone substrates unmapped","Strain-specific behavior not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["MYST domain architecture: MYST catalytic domain, atypical C2HC zinc finger, and chromodomain [#0]","Localizes to the ATM kinase gene locus and elevates ATM kinase protein and phospho-H2AX [#2]","Overexpression of catalytically active TgMYST-B slows parasite growth and protects against DNA-alkylating agents; catalytic mutant abolishes both effects [#1]","Slow-growth phenotype reversed by ATM kinase or KAT inhibitors, placing TgMYST-B upstream of ATM kinase [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"16339723","id":"PMC_16339723","title":"MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii.","date":"2005","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/16339723","citation_count":36,"is_preprint":false},{"pmid":"20159970","id":"PMC_20159970","title":"MYST family lysine acetyltransferase facilitates ataxia telangiectasia mutated (ATM) kinase-mediated DNA damage response in Toxoplasma gondii.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20159970","citation_count":31,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3514,"output_tokens":1131,"usd":0.013754,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6014,"output_tokens":2269,"usd":0.043397,"stage2_stop_reason":"end_turn"},"total_usd":0.057151,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"TgMYST-A (a MYST family HAT paralog characterized in the same study as TgMYST-B) possesses a canonical MYST HAT catalytic domain, an atypical C2HC zinc finger, and a chromodomain; recombinant TgMYST-A acetylates histone H4 in vitro at lysines 5, 8, 12, and 16. TgMYST-B was identified as a second MYST homologue with a ~7.0-kb mRNA encoding a MYST-family lysine acetyltransferase with the same domain architecture (MYST catalytic domain, C2HC zinc finger, chromodomain).\",\n      \"method\": \"In vitro histone acetyltransferase assay with recombinant protein; bioinformatics domain analysis; mRNA transcript characterization\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay performed for TgMYST-A; TgMYST-B was identified and domain-annotated but enzymatic activity not directly assayed in this paper; single lab\",\n      \"pmids\": [\"16339723\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"TgMYST-B localizes to the parasite nucleus and acetylates histones in vivo. Overexpression of catalytically active recombinant TgMYST-B reduces parasite growth rate in vitro and confers protection from a DNA-alkylating agent, whereas expression of a catalytic mutant TgMYST-B produces no growth defect and fails to protect against DNA damage, establishing that the acetyltransferase activity is required for these effects.\",\n      \"method\": \"Overexpression of wild-type and catalytic-mutant tagged TgMYST-B; in vitro growth assay; DNA-alkylating agent challenge; nuclear localization confirmed by subcellular fractionation/imaging\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — active-site mutagenesis distinguishes enzymatic from non-enzymatic effects, combined with growth and DNA-damage phenotypic readouts in a single focused study\",\n      \"pmids\": [\"20159970\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Parasites overexpressing TgMYST-B display increased levels of ATM kinase protein and phosphorylated H2AX (a DNA-damage marker), and TgMYST-B localizes to the ATM kinase gene locus, indicating TgMYST-B promotes ATM kinase expression as part of the DNA damage response. Pharmacological inhibition of ATM kinase or KATs reverses the slow-growth phenotype caused by TgMYST-B overexpression, placing TgMYST-B upstream of ATM kinase in this pathway.\",\n      \"method\": \"Immunoblot for ATM and phospho-H2AX in overexpression parasites; ChIP-localization of TgMYST-B to the ATM kinase gene; pharmacological epistasis with ATM kinase and KAT inhibitors\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (ChIP, immunoblot, pharmacological epistasis) in a single lab study\",\n      \"pmids\": [\"20159970\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgMYST-B is a nuclear MYST-family lysine acetyltransferase in Toxoplasma gondii that acetylates histones, promotes ATM kinase gene expression by localizing to its locus, and thereby facilitates the ATM kinase-mediated DNA damage response; its acetyltransferase catalytic activity is required for both its growth-regulatory effect and protection against DNA-alkylating agents.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgMYST-B is a nuclear MYST-family lysine acetyltransferase of Toxoplasma gondii that couples histone acetylation to the parasite DNA damage response [#1, #2]. It shares the MYST domain architecture of its paralog TgMYST-A — a MYST catalytic domain, an atypical C2HC zinc finger, and a chromodomain — and was identified from a ~7.0-kb mRNA [#0]. TgMYST-B localizes to the nucleus and acetylates histones in vivo; overexpression of the catalytically active enzyme slows parasite growth and protects against a DNA-alkylating agent, while a catalytic-site mutant abolishes both effects, establishing that acetyltransferase activity is required [#1]. Mechanistically, TgMYST-B localizes to the ATM kinase gene locus and elevates ATM kinase protein and phospho-H2AX levels, and pharmacological inhibition of either ATM kinase or KATs reverses the overexpression-induced slow growth, placing TgMYST-B upstream of ATM kinase in the DNA damage response [#2]. Beyond this histone-acetylation-to-ATM axis, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"The question of whether Toxoplasma encodes MYST-family acetyltransferases was answered by identifying two homologues, defining TgMYST-B as a MYST-family lysine acetyltransferase with a conserved catalytic-domain/zinc-finger/chromodomain architecture.\",\n      \"evidence\": \"Bioinformatic domain analysis and mRNA transcript characterization, with in vitro HAT assay on the paralog TgMYST-A acetylating histone H4\",\n      \"pmids\": [\"16339723\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"TgMYST-B's own enzymatic activity was not directly assayed in this study\",\n        \"No in vivo substrate or localization established here\",\n        \"Histone-lysine specificity of TgMYST-B not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether TgMYST-B is a functional nuclear acetyltransferase and whether its catalytic activity drives phenotypes was resolved by showing it is nuclear, acetylates histones in vivo, and that only the catalytically active form slows growth and protects against DNA alkylation.\",\n      \"evidence\": \"Overexpression of wild-type versus catalytic-mutant tagged TgMYST-B with growth assays, DNA-alkylating challenge, and subcellular localization\",\n      \"pmids\": [\"20159970\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Endogenous (non-overexpression) function not tested by knockout/knockdown\",\n        \"Direct histone-lysine targets in vivo not mapped\",\n        \"Mechanism linking acetylation to growth suppression unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The pathway connecting TgMYST-B acetyltransferase activity to the DNA damage response was defined by placing it upstream of ATM kinase at the transcriptional level.\",\n      \"evidence\": \"Immunoblot for ATM and phospho-H2AX, ChIP-localization of TgMYST-B to the ATM kinase gene, and pharmacological epistasis with ATM kinase and KAT inhibitors in overexpression parasites\",\n      \"pmids\": [\"20159970\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct transcriptional activation of the ATM locus versus indirect effect not distinguished\",\n        \"Whether histone acetylation at the ATM locus is the causal event not shown\",\n        \"Physiological DNA-damage signal that engages TgMYST-B unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous role of TgMYST-B and its full genomic acetylation targets remain unresolved beyond overexpression phenotypes.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function (knockout/conditional) analysis in the corpus\",\n        \"Genome-wide acetylation targets and non-histone substrates unmapped\",\n        \"Strain-specific behavior not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004402\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0043966\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006974\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0045893\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"MYST domain architecture: MYST catalytic domain, atypical C2HC zinc finger, and chromodomain [#0]\",\n      \"Localizes to the ATM kinase gene locus and elevates ATM kinase protein and phospho-H2AX [#2]\",\n      \"Overexpression of catalytically active TgMYST-B slows parasite growth and protects against DNA-alkylating agents; catalytic mutant abolishes both effects [#1]\",\n      \"Slow-growth phenotype reversed by ATM kinase or KAT inhibitors, placing TgMYST-B upstream of ATM kinase [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_207080","name":"MYSTB","product":"histone lysine acetyltransferase MYST-B","uniprot_acc":"S8ESL0","chromosome":"TGME49_chrX","start_pos":7373449},{"strain":"GT1","gene_id":"TGGT1_207080","name":null,"product":"histone lysine acetyltransferase MYST-B","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":7247562},{"strain":"RH88","gene_id":"TGRH88_038490","name":null,"product":"histone lysine acetyltransferase MYST-B","uniprot_acc":null,"chromosome":"CM023091","start_pos":119524},{"strain":"VEG","gene_id":"TGVEG_207080","name":null,"product":"histone lysine acetyltransferase MYST-B","uniprot_acc":"B9QQG8","chromosome":"TGVEG_chrX","start_pos":7303168}]}