{"gene":"PF3D7_0216000","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2023,"finding":"SNF2 (gSNF2, PF3D7_0216000), an SNF2-like chromatin remodeling ATPase, is essential for male gametocyte differentiation into gametes; its disruption abolishes male gamete development. ChIP-seq showed SNF2 is recruited upstream of male-specific genes through a five-base male-specific cis-acting element (TGTCT), and ATAC-seq demonstrated that loss of SNF2 reduces nucleosome-free regions upstream of these target genes, with consequent decreased expression of over a hundred male-specific genes.","method":"Genetic disruption (knockout), ChIP-seq, ATAC-seq, transcriptome analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype, two orthogonal genome-wide methods (ChIP-seq and ATAC-seq) establishing mechanistic link between SNF2 binding, chromatin accessibility, and target gene expression","pmids":["37155862"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"SNF2 (gSNF2, PF3D7_0216000) forms a complex with PbARID, a putative subunit of the SWI/SNF chromatin remodeling complex, at the male cis-regulatory element TGTCT during gametocyte development. ChIP-seq of PbARID in gsnf2-knockout parasites revealed that PbARID can also associate independently with a distinct cis-regulatory element (TGCACA), indicating SNF2 is required for PbARID recruitment specifically to TGTCT-containing loci.","method":"ChIP-seq (PbARID in wild-type and gsnf2-knockout parasites), RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins), DNA-binding assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal ChIP-seq in knockout background plus RIME proteomic interaction data and DNA-binding assays, multiple orthogonal methods in a single rigorous study","pmids":["38554111"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"SNF2 (PF3D7_0216000) is an ATPase subunit of the SWI/SNF chromatin remodeling complex in Plasmodium that is recruited—together with PbARID—to a five-base male-specific cis-element (TGTCT) upstream of male gametocyte genes, where it opens chromatin (increases nucleosome-free regions) to drive expression of over a hundred male-specific genes and is thereby essential for male gametocyte differentiation into gametes."},"narrative":{"mechanistic_narrative":"SNF2 (PF3D7_0216000) is an SNF2-like chromatin remodeling ATPase that drives the male-specific transcriptional program required for gametocyte differentiation into gametes in Plasmodium [PMID:37155862]. In P. berghei, SNF2 is recruited to a five-base male-specific cis-acting element (TGTCT) upstream of male gametocyte genes, where it increases chromatin accessibility (nucleosome-free regions) and thereby activates expression of over a hundred male-specific genes; genetic disruption abolishes male gamete development [PMID:37155862]. SNF2 acts within a SWI/SNF-type complex together with PbARID, and it is specifically required to recruit PbARID to TGTCT-containing loci—in gsnf2-knockout parasites PbARID retains binding to a distinct element (TGCACA) but loses TGTCT association [PMID:38554111]. Beyond this male-gametocyte chromatin-opening role defined in P. berghei, no further mechanistic detail—including biochemical characterization of the ATPase activity itself—has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing whether a chromatin remodeler controls male gametocyte development, this work showed SNF2 is essential for male gamete formation and links its recruitment to a specific cis-element and to chromatin opening at target genes.","evidence":"Genetic knockout with defined cellular phenotype plus ChIP-seq, ATAC-seq, and transcriptome analysis in P. berghei","pmids":["37155862"],"confidence":"High","gaps":["ATPase catalytic activity and its requirement for chromatin opening not directly tested","How SNF2 achieves TGTCT sequence specificity (direct DNA contact vs. partner-mediated) unresolved","Findings established in P. berghei; not demonstrated for the P. falciparum ortholog"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"Addressing how SNF2 functions within a complex, this work showed SNF2 partners with PbARID and is required for PbARID recruitment specifically to TGTCT loci, defining the hierarchy of assembly at the male cis-element.","evidence":"ChIP-seq of PbARID in wild-type and gsnf2-knockout parasites, RIME proteomics, and DNA-binding assays in P. berghei","pmids":["38554111"],"confidence":"High","gaps":["Full subunit composition of the SWI/SNF complex containing SNF2 not defined","Whether SNF2 or PbARID directly contacts the TGTCT element not resolved","Functional significance of PbARID's SNF2-independent binding to TGCACA not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The biochemical ATPase/remodeling activity of SNF2 and the mechanism of its sequence-specific targeting remain to be defined.","evidence":"","pmids":[],"confidence":"High","gaps":["No in vitro reconstitution or direct demonstration of nucleosome remodeling by SNF2","Structural basis of TGTCT recognition unknown","Role, if any, in the P. falciparum life cycle uncharacterized in this corpus"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SWI/SNF chromatin remodeling complex (with PbARID)"],"partners":["PBARID"],"other_free_text":["Recruited to the male-specific cis-regulatory element TGTCT upstream of male gametocyte genes (P. berghei) [#0, #1]","Required for recruitment of PbARID to TGTCT loci; PbARID binds TGCACA independently of SNF2 [#1]","Loss reduces nucleosome-free regions and downregulates >100 male-specific genes; essential for male gamete development (P. berghei) [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"37155862","id":"PMC_37155862","title":"Differentiation of Plasmodium male gametocytes is initiated by the recruitment of a chromatin remodeler to a male-specific cis-element.","date":"2023","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/37155862","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["gSNF2","SNF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38554111","id":"PMC_38554111","title":"PbARID-associated chromatin remodeling events are essential for gametocyte development in Plasmodium.","date":"2024","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/38554111","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["gSNF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3726,"output_tokens":815,"usd":0.011702,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5500,"output_tokens":1711,"usd":0.035138,"stage2_stop_reason":"end_turn"},"total_usd":0.04684,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"SNF2 (gSNF2, PF3D7_0216000), an SNF2-like chromatin remodeling ATPase, is essential for male gametocyte differentiation into gametes; its disruption abolishes male gamete development. ChIP-seq showed SNF2 is recruited upstream of male-specific genes through a five-base male-specific cis-acting element (TGTCT), and ATAC-seq demonstrated that loss of SNF2 reduces nucleosome-free regions upstream of these target genes, with consequent decreased expression of over a hundred male-specific genes.\",\n      \"method\": \"Genetic disruption (knockout), ChIP-seq, ATAC-seq, transcriptome analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype, two orthogonal genome-wide methods (ChIP-seq and ATAC-seq) establishing mechanistic link between SNF2 binding, chromatin accessibility, and target gene expression\",\n      \"pmids\": [\"37155862\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SNF2 (gSNF2, PF3D7_0216000) forms a complex with PbARID, a putative subunit of the SWI/SNF chromatin remodeling complex, at the male cis-regulatory element TGTCT during gametocyte development. ChIP-seq of PbARID in gsnf2-knockout parasites revealed that PbARID can also associate independently with a distinct cis-regulatory element (TGCACA), indicating SNF2 is required for PbARID recruitment specifically to TGTCT-containing loci.\",\n      \"method\": \"ChIP-seq (PbARID in wild-type and gsnf2-knockout parasites), RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins), DNA-binding assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal ChIP-seq in knockout background plus RIME proteomic interaction data and DNA-binding assays, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"38554111\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SNF2 (PF3D7_0216000) is an ATPase subunit of the SWI/SNF chromatin remodeling complex in Plasmodium that is recruited—together with PbARID—to a five-base male-specific cis-element (TGTCT) upstream of male gametocyte genes, where it opens chromatin (increases nucleosome-free regions) to drive expression of over a hundred male-specific genes and is thereby essential for male gametocyte differentiation into gametes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNF2 (PF3D7_0216000) is an SNF2-like chromatin remodeling ATPase that drives the male-specific transcriptional program required for gametocyte differentiation into gametes in Plasmodium [#0]. In P. berghei, SNF2 is recruited to a five-base male-specific cis-acting element (TGTCT) upstream of male gametocyte genes, where it increases chromatin accessibility (nucleosome-free regions) and thereby activates expression of over a hundred male-specific genes; genetic disruption abolishes male gamete development [#0]. SNF2 acts within a SWI/SNF-type complex together with PbARID, and it is specifically required to recruit PbARID to TGTCT-containing loci\\u2014in gsnf2-knockout parasites PbARID retains binding to a distinct element (TGCACA) but loses TGTCT association [#1]. Beyond this male-gametocyte chromatin-opening role defined in P. berghei, no further mechanistic detail\\u2014including biochemical characterization of the ATPase activity itself\\u2014has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing whether a chromatin remodeler controls male gametocyte development, this work showed SNF2 is essential for male gamete formation and links its recruitment to a specific cis-element and to chromatin opening at target genes.\",\n      \"evidence\": \"Genetic knockout with defined cellular phenotype plus ChIP-seq, ATAC-seq, and transcriptome analysis in P. berghei\",\n      \"pmids\": [\"37155862\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"ATPase catalytic activity and its requirement for chromatin opening not directly tested\",\n        \"How SNF2 achieves TGTCT sequence specificity (direct DNA contact vs. partner-mediated) unresolved\",\n        \"Findings established in P. berghei; not demonstrated for the P. falciparum ortholog\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Addressing how SNF2 functions within a complex, this work showed SNF2 partners with PbARID and is required for PbARID recruitment specifically to TGTCT loci, defining the hierarchy of assembly at the male cis-element.\",\n      \"evidence\": \"ChIP-seq of PbARID in wild-type and gsnf2-knockout parasites, RIME proteomics, and DNA-binding assays in P. berghei\",\n      \"pmids\": [\"38554111\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Full subunit composition of the SWI/SNF complex containing SNF2 not defined\",\n        \"Whether SNF2 or PbARID directly contacts the TGTCT element not resolved\",\n        \"Functional significance of PbARID's SNF2-independent binding to TGCACA not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical ATPase/remodeling activity of SNF2 and the mechanism of its sequence-specific targeting remain to be defined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No in vitro reconstitution or direct demonstration of nucleosome remodeling by SNF2\",\n        \"Structural basis of TGTCT recognition unknown\",\n        \"Role, if any, in the P. falciparum life cycle uncharacterized in this corpus\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0006338\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003678\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0045944\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0007140\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"SWI/SNF chromatin remodeling complex (with PbARID)\"\n    ],\n    \"partners\": [\n      \"PbARID\"\n    ],\n    \"other_free_text\": [\n      \"Recruited to the male-specific cis-regulatory element TGTCT upstream of male gametocyte genes (P. berghei) [#0, #1]\",\n      \"Required for recruitment of PbARID to TGTCT loci; PbARID binds TGCACA independently of SNF2 [#1]\",\n      \"Loss reduces nucleosome-free regions and downregulates >100 male-specific genes; essential for male gamete development (P. berghei) [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0216000","name":null,"product":"SNF2-like chromatin remodeling ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0312700","name":null,"product":"DEAD/DEAH box helicase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0404900","name":null,"product":"DEAD/DEAH box helicase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"gSNF2","evaluation":null}