{"gene":"TG_217700","gene_symbol":"AP2XII2","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2020,"finding":"AP2XII-2 is a cell cycle-regulated ApiAP2 that associates with AP2IX-4 and is a component of the MORC transcriptional repressor complex. Peak expression of AP2XII-2 protein occurs during S/M phase of the tachyzoite cell cycle.","method":"Co-immunoprecipitation / protein pulldown, cell cycle staging by immunofluorescence","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP identifying complex membership, single lab, two orthogonal methods (co-IP and cell cycle staging)","pmids":["32938695"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"Loss of AP2XII-2 results in slowed tachyzoite growth due to a delay in S-phase progression, establishing AP2XII-2 as required for proper cell cycle progression through S-phase.","method":"Conditional gene knockdown with cell cycle analysis (flow cytometry / BrdU incorporation)","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined cell cycle phenotype, single lab, multiple readouts","pmids":["32938695"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"Depletion of AP2XII-2 increased the frequency of bradyzoite differentiation in vitro, indicating AP2XII-2 plays a role in suppressing the transition from tachyzoites to bradyzoites.","method":"Conditional gene knockdown with differentiation assay (bradyzoite marker expression)","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined developmental phenotype, single lab","pmids":["32938695"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"AP2XII-2 is targeted to genomic loci associated with sexually committed parasites and co-occupies promoters with epigenetic repressors HDAC3 and MORC, establishing AP2XII-2 as a component of the transcriptional silencing machinery at sexual-stage gene loci.","method":"CUT&Tag (Cleavage Under Targets and Tagmentation) chromatin profiling","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct chromatin binding assay (CUT&Tag), single lab, genome-wide resolution","pmids":["36786611"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"AP2XII-2 is required for silencing of two major sexual development-associated genes: AP2X-10 (a sexual stage-specific AP2 transcription factor) and AAH1 (amino acid hydroxylase required for infectious oocyst construction). Despite widespread promoter association, AP2XII-2 controls a relatively restricted set of target genes.","method":"CUT&Tag combined with transcriptomic analysis upon conditional depletion of AP2XII-2","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide chromatin and transcriptomic readouts combined, single lab","pmids":["36786611"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"finding":"Conditional depletion of AP2XII-2 (alongside AP2XII-1) enables tachyzoite-to-merozoite differentiation in vitro, and the transition is associated with a switch from endodyogeny to endopolygeny during cell division. This establishes AP2XII-2 as a repressor of the pre-sexual developmental program.","method":"Conditional depletion, expansion microscopy, quantitative cell division analysis, stage-specific markers","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with morphological and division-mode phenotype characterization, single study","pmids":["42153709"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"AP2XII-2 (as one of ~24 AP2 transcription factors) exhibits a cell cycle-regulated expression pattern in dividing tachyzoites, with sharp peaks of protein expression correlating with its mRNA peaks, placing it in the S/M-subtranscriptome wave during tachyzoite division.","method":"Genome-wide transcriptome profiling coupled with protein expression timing analysis across the cell cycle","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Moderate — expression-level evidence from a large-scale cell cycle transcriptome study; no direct functional experiment on AP2XII-2 specifically","pmids":["20865045"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AP2XII-2 is a cell cycle-regulated ApiAP2 transcription factor that peaks in S/M phase of the tachyzoite cycle, forms part of the MORC transcriptional repressor complex (together with AP2IX-4, HDAC3, and MORC), directly silences a subset of sexual-stage genes (including AP2X-10 and AAH1) by binding their promoters, is required for proper S-phase progression in tachyzoites, suppresses bradyzoite differentiation during asexual growth, and—together with AP2XII-1—acts as a key repressor of presexual/merozoite commitment, such that their combined depletion triggers a full epigenetic switch from tachyzoite to merozoite (pre-sexual) development in vitro."},"narrative":{"mechanistic_narrative":"AP2XII-2 is a cell cycle-regulated ApiAP2 transcription factor in Toxoplasma gondii that functions as a transcriptional repressor coordinating tachyzoite cell-cycle progression with the silencing of developmental gene programs [PMID:32938695, PMID:36786611]. Its protein expression peaks during S/M phase of the tachyzoite cycle, and it operates as a component of the MORC repressor complex, associating with AP2IX-4 and co-occupying promoters with the epigenetic silencers HDAC3 and MORC [PMID:32938695, PMID:36786611]. At the chromatin level AP2XII-2 is targeted to loci associated with sexually committed parasites and directly silences a restricted set of sexual-stage genes, including the sexual-stage transcription factor AP2X-10 and the oocyst-biogenesis hydroxylase AAH1 [PMID:36786611]. Functionally, loss of AP2XII-2 delays S-phase progression and slows tachyzoite growth, and its depletion de-represses bradyzoite differentiation, marking it as a suppressor of stage conversion during asexual growth [PMID:32938695]. Together with AP2XII-1, AP2XII-2 restrains the pre-sexual developmental program: their combined depletion permits a tachyzoite-to-merozoite transition accompanied by a switch from endodyogeny to endopolygeny [PMID:42153709].","teleology":[{"year":2010,"claim":"Establishing that AP2XII-2 is expressed periodically during the tachyzoite cycle raised the question of whether it couples transcription to cell division, placing it in the S/M expression wave.","evidence":"Genome-wide cell cycle transcriptome profiling with protein expression timing across dividing tachyzoites","pmids":["20865045"],"confidence":"Low","gaps":["Expression-level correlation only, with no direct functional test of AP2XII-2","Does not establish DNA-binding targets or complex membership"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"To define AP2XII-2's molecular role, its physical partners and cell-cycle timing were determined, showing it is an S/M-phase MORC-complex component associated with AP2IX-4.","evidence":"Reciprocal co-immunoprecipitation and cell cycle staging by immunofluorescence in tachyzoites","pmids":["32938695"],"confidence":"Medium","gaps":["Direct genomic binding sites not resolved by co-IP","Stoichiometry and architecture of AP2XII-2 within the MORC complex unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Conditional knockdown addressed whether AP2XII-2 has a functional requirement, revealing a delay in S-phase progression and a de-repression of bradyzoite differentiation.","evidence":"Conditional gene knockdown with flow cytometry/BrdU cell cycle analysis and bradyzoite marker differentiation assays","pmids":["32938695"],"confidence":"Medium","gaps":["Mechanistic link between the S-phase defect and the transcriptional repressor role not resolved","Direct target genes driving the bradyzoite phenotype not identified in this study"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Chromatin profiling asked where AP2XII-2 acts on the genome, showing it occupies sexually-committed loci alongside HDAC3 and MORC and directly silences a restricted set of sexual-stage genes.","evidence":"CUT&Tag chromatin profiling combined with transcriptomics upon conditional depletion, identifying AP2X-10 and AAH1 as targets","pmids":["36786611"],"confidence":"Medium","gaps":["Why widespread promoter binding controls only a narrow target set is unexplained","Sequence determinants of AP2XII-2 DNA recognition not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"claim":"Combined depletion of AP2XII-2 with AP2XII-1 tested AP2XII-2's role in pre-sexual commitment, showing it represses the tachyzoite-to-merozoite transition and a coupled switch from endodyogeny to endopolygeny.","evidence":"Conditional depletion with expansion microscopy, quantitative cell division analysis, and stage-specific markers","pmids":["42153709"],"confidence":"Medium","gaps":["Relative contributions of AP2XII-2 versus AP2XII-1 to the phenotype not separated","How repression is coupled to the endodyogeny-to-endopolygeny division switch unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MORC transcriptional repressor complex (with AP2IX-4, HDAC3, MORC)"],"partners":["AP2IX-4","HDAC3","MORC","AP2XII-1"],"other_free_text":["Silences sexual-stage target genes AP2X-10 (sexual-stage AP2 transcription factor) and AAH1 (amino acid hydroxylase for oocyst construction) [#4]","Depletion permits tachyzoite-to-merozoite transition with a switch from endodyogeny to endopolygeny [#6]","Identified as an arginine monomethylated protein, a candidate PRMT1 substrate [#8]"]},"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":"36786611","id":"PMC_36786611","title":"Toxoplasma gondii AP2XII-2 Contributes to Transcriptional Repression for Sexual Commitment.","date":"2023","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/36786611","citation_count":32,"is_preprint":false},{"pmid":"32938695","id":"PMC_32938695","title":"Toxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycle.","date":"2020","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/32938695","citation_count":27,"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":"42153709","id":"PMC_42153709","title":"Proliferating toward sex: characterization of cell division of Toxoplasma gondii's pre-sexual stages.","date":"2026","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/42153709","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16027,"output_tokens":2216,"usd":0.040661,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7735,"output_tokens":3381,"usd":0.0616,"stage2_stop_reason":"end_turn"},"total_usd":0.102261,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"summary amended"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"AP2XII-2 is a cell cycle-regulated ApiAP2 that associates with AP2IX-4 and is a component of the MORC transcriptional repressor complex. Peak expression of AP2XII-2 protein occurs during S/M phase of the tachyzoite cell cycle.\",\n      \"method\": \"Co-immunoprecipitation / protein pulldown, cell cycle staging by immunofluorescence\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP identifying complex membership, single lab, two orthogonal methods (co-IP and cell cycle staging)\",\n      \"pmids\": [\"32938695\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Loss of AP2XII-2 results in slowed tachyzoite growth due to a delay in S-phase progression, establishing AP2XII-2 as required for proper cell cycle progression through S-phase.\",\n      \"method\": \"Conditional gene knockdown with cell cycle analysis (flow cytometry / BrdU incorporation)\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined cell cycle phenotype, single lab, multiple readouts\",\n      \"pmids\": [\"32938695\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Depletion of AP2XII-2 increased the frequency of bradyzoite differentiation in vitro, indicating AP2XII-2 plays a role in suppressing the transition from tachyzoites to bradyzoites.\",\n      \"method\": \"Conditional gene knockdown with differentiation assay (bradyzoite marker expression)\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined developmental phenotype, single lab\",\n      \"pmids\": [\"32938695\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"AP2XII-2 is targeted to genomic loci associated with sexually committed parasites and co-occupies promoters with epigenetic repressors HDAC3 and MORC, establishing AP2XII-2 as a component of the transcriptional silencing machinery at sexual-stage gene loci.\",\n      \"method\": \"CUT&Tag (Cleavage Under Targets and Tagmentation) chromatin profiling\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct chromatin binding assay (CUT&Tag), single lab, genome-wide resolution\",\n      \"pmids\": [\"36786611\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"AP2XII-2 is required for silencing of two major sexual development-associated genes: AP2X-10 (a sexual stage-specific AP2 transcription factor) and AAH1 (amino acid hydroxylase required for infectious oocyst construction). Despite widespread promoter association, AP2XII-2 controls a relatively restricted set of target genes.\",\n      \"method\": \"CUT&Tag combined with transcriptomic analysis upon conditional depletion of AP2XII-2\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide chromatin and transcriptomic readouts combined, single lab\",\n      \"pmids\": [\"36786611\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Simultaneous conditional depletion of AP2XII-1 and AP2XI-2 (not AP2XII-2 alone) leads to a full transcriptional and morphological transition from tachyzoites to merozoites (pre-sexual stages) in vitro. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite gene promoters and recruit MORC and HDAC3 to restrict chromatin accessibility.\",\n      \"method\": \"Conditional double-knockdown, ChIP/chromatin accessibility assays, transcriptomics, immunofluorescence with stage-specific markers\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification, chromatin accessibility, transcriptomics, and morphological validation; independently reported in preprint and peer-reviewed paper with multiple orthogonal methods\",\n      \"pmids\": [\"38093015\", \"36711883\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Conditional depletion of AP2XII-2 (alongside AP2XII-1) enables tachyzoite-to-merozoite differentiation in vitro, and the transition is associated with a switch from endodyogeny to endopolygeny during cell division. This establishes AP2XII-2 as a repressor of the pre-sexual developmental program.\",\n      \"method\": \"Conditional depletion, expansion microscopy, quantitative cell division analysis, stage-specific markers\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with morphological and division-mode phenotype characterization, single study\",\n      \"pmids\": [\"42153709\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"AP2XII-2 (as one of ~24 AP2 transcription factors) exhibits a cell cycle-regulated expression pattern in dividing tachyzoites, with sharp peaks of protein expression correlating with its mRNA peaks, placing it in the S/M-subtranscriptome wave during tachyzoite division.\",\n      \"method\": \"Genome-wide transcriptome profiling coupled with protein expression timing analysis across the cell cycle\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — expression-level evidence from a large-scale cell cycle transcriptome study; no direct functional experiment on AP2XII-2 specifically\",\n      \"pmids\": [\"20865045\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"AP2XII-2 was identified as an arginine monomethylated protein in T. gondii, suggesting it may be a substrate of PRMT1-mediated arginine methylation.\",\n      \"method\": \"Affinity purification with anti-monomethylarginine antibodies followed by mass spectrometry\",\n      \"journal\": \"Molecular & cellular proteomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proteomics screen, no functional follow-up on AP2XII-2 specifically\",\n      \"pmids\": [\"28143887\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"AP2XII-2 is a cell cycle-regulated ApiAP2 transcription factor that peaks in S/M phase of the tachyzoite cycle, forms part of the MORC transcriptional repressor complex (together with AP2IX-4, HDAC3, and MORC), directly silences a subset of sexual-stage genes (including AP2X-10 and AAH1) by binding their promoters, is required for proper S-phase progression in tachyzoites, suppresses bradyzoite differentiation during asexual growth, and—together with AP2XII-1—acts as a key repressor of presexual/merozoite commitment, such that their combined depletion triggers a full epigenetic switch from tachyzoite to merozoite (pre-sexual) development in vitro.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"AP2XII-2 is a cell cycle-regulated ApiAP2 transcription factor in Toxoplasma gondii that functions as a transcriptional repressor coordinating tachyzoite cell-cycle progression with the silencing of developmental gene programs [#0, #4]. Its protein expression peaks during S/M phase of the tachyzoite cycle, and it operates as a component of the MORC repressor complex, associating with AP2IX-4 and co-occupying promoters with the epigenetic silencers HDAC3 and MORC [#0, #3]. At the chromatin level AP2XII-2 is targeted to loci associated with sexually committed parasites and directly silences a restricted set of sexual-stage genes, including the sexual-stage transcription factor AP2X-10 and the oocyst-biogenesis hydroxylase AAH1 [#3, #4]. Functionally, loss of AP2XII-2 delays S-phase progression and slows tachyzoite growth, and its depletion de-represses bradyzoite differentiation, marking it as a suppressor of stage conversion during asexual growth [#1, #2]. Together with AP2XII-1, AP2XII-2 restrains the pre-sexual developmental program: their combined depletion permits a tachyzoite-to-merozoite transition accompanied by a switch from endodyogeny to endopolygeny [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Establishing that AP2XII-2 is expressed periodically during the tachyzoite cycle raised the question of whether it couples transcription to cell division, placing it in the S/M expression wave.\",\n      \"evidence\": \"Genome-wide cell cycle transcriptome profiling with protein expression timing across dividing tachyzoites\",\n      \"pmids\": [\"20865045\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Expression-level correlation only, with no direct functional test of AP2XII-2\", \"Does not establish DNA-binding targets or complex membership\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"A proteomic screen asked whether AP2XII-2 is post-translationally modified, identifying it as an arginine monomethylated protein and a candidate PRMT1 substrate.\",\n      \"evidence\": \"Anti-monomethylarginine affinity purification followed by mass spectrometry\",\n      \"pmids\": [\"28143887\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single proteomics screen with no functional follow-up on the modification\", \"Role of methylation in AP2XII-2 activity or complex assembly unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To define AP2XII-2's molecular role, its physical partners and cell-cycle timing were determined, showing it is an S/M-phase MORC-complex component associated with AP2IX-4.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation and cell cycle staging by immunofluorescence in tachyzoites\",\n      \"pmids\": [\"32938695\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct genomic binding sites not resolved by co-IP\", \"Stoichiometry and architecture of AP2XII-2 within the MORC complex unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Conditional knockdown addressed whether AP2XII-2 has a functional requirement, revealing a delay in S-phase progression and a de-repression of bradyzoite differentiation.\",\n      \"evidence\": \"Conditional gene knockdown with flow cytometry/BrdU cell cycle analysis and bradyzoite marker differentiation assays\",\n      \"pmids\": [\"32938695\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between the S-phase defect and the transcriptional repressor role not resolved\", \"Direct target genes driving the bradyzoite phenotype not identified in this study\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Chromatin profiling asked where AP2XII-2 acts on the genome, showing it occupies sexually-committed loci alongside HDAC3 and MORC and directly silences a restricted set of sexual-stage genes.\",\n      \"evidence\": \"CUT&Tag chromatin profiling combined with transcriptomics upon conditional depletion, identifying AP2X-10 and AAH1 as targets\",\n      \"pmids\": [\"36786611\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Why widespread promoter binding controls only a narrow target set is unexplained\", \"Sequence determinants of AP2XII-2 DNA recognition not defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Work on the paralogous repressor module established that AP2XII-1/AP2XI-2 heterodimers recruit MORC/HDAC3 to restrict merozoite gene chromatin, providing the mechanistic framework for pre-sexual repression that AP2XII-2 participates in.\",\n      \"evidence\": \"Conditional double-knockdown with ChIP/chromatin accessibility assays, transcriptomics, and stage-marker immunofluorescence\",\n      \"pmids\": [\"38093015\", \"36711883\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"This transition was driven by AP2XII-1/AP2XI-2, not by AP2XII-2 in this study\", \"Whether AP2XII-2 physically joins these heterodimers not established here\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Combined depletion of AP2XII-2 with AP2XII-1 tested AP2XII-2's role in pre-sexual commitment, showing it represses the tachyzoite-to-merozoite transition and a coupled switch from endodyogeny to endopolygeny.\",\n      \"evidence\": \"Conditional depletion with expansion microscopy, quantitative cell division analysis, and stage-specific markers\",\n      \"pmids\": [\"42153709\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative contributions of AP2XII-2 versus AP2XII-1 to the phenotype not separated\", \"How repression is coupled to the endodyogeny-to-endopolygeny division switch unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How AP2XII-2's S/M-phase timing, MORC-complex recruitment, DNA-sequence targeting, and arginine methylation are integrated to control the restricted silencing of sexual/pre-sexual genes remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural or DNA-motif model for AP2XII-2 target selection\", \"Functional significance of arginine monomethylation untested\", \"Mechanism linking S-phase cell cycle role to developmental repression unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003700\", \"supporting_discovery_ids\": [0, 4, 7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000122\", \"supporting_discovery_ids\": [3, 4, 6], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [1, 7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0030154\", \"supporting_discovery_ids\": [2, 6], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"MORC transcriptional repressor complex (with AP2IX-4, HDAC3, MORC)\"],\n    \"partners\": [\"AP2IX-4\", \"HDAC3\", \"MORC\", \"AP2XII-1\"],\n    \"other_free_text\": [\n      \"Silences sexual-stage target genes AP2X-10 (sexual-stage AP2 transcription factor) and AAH1 (amino acid hydroxylase for oocyst construction) [#4]\",\n      \"Depletion permits tachyzoite-to-merozoite transition with a switch from endodyogeny to endopolygeny [#6]\",\n      \"Identified as an arginine monomethylated protein, a candidate PRMT1 substrate [#8]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_217700","name":"AP2XII2","product":"AP2 domain transcription factor AP2XII-2","uniprot_acc":"S8EN98","chromosome":"TGME49_chrXII","start_pos":2025270},{"strain":"GT1","gene_id":"TGGT1_217700","name":null,"product":"AP2 domain transcription factor AP2XII-2","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":1965064},{"strain":"RH88","gene_id":"TGRH88_059640","name":null,"product":"AP2 domain transcription factor AP2XII-2","uniprot_acc":null,"chromosome":"CM023093","start_pos":2036888},{"strain":"VEG","gene_id":"TGVEG_217700","name":null,"product":"AP2 domain transcription factor AP2XII-2","uniprot_acc":"A0A125YL42","chromosome":"TGVEG_chrXII","start_pos":1998765}]}