{"gene":"PF3D7_0320900","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2010,"finding":"H2A.Z is a constant, ubiquitous feature of euchromatic intergenic regions throughout the intraerythrocytic cycle in P. falciparum, and almost perfectly colocalizes with H3K9ac and H3K4me3, suggesting these marks are preferentially deposited on H2A.Z-containing nucleosomes. H2A.Z stably defines intergenic regions and provides a platform for dynamic assembly of epigenetic and transcription-related complexes.","method":"Genome-wide ChIP-seq (next-generation sequencing with linear amplification method) across intraerythrocytic development, combined with RNA-seq at 8 time-points","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide ChIP-seq with multiple orthogonal marks (H3K9ac, H3K4me3) and RNA-seq, providing comprehensive mechanistic placement of H2A.Z in the P. falciparum epigenome","pmids":["21187892"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"Mass spectrometry identified a novel pattern of lysine modifications on H2A.Z in P. falciparum. The variant histone H2A.Z is encoded in the P. falciparum genome and its expression decreases in mid- or late trophozoite stages, in contrast to canonical histones which peak at late trophozoite.","method":"Mass spectrometry, real-time RT-PCR, immunoblotting","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry and immunoblotting in a single study providing direct PTM identification and expression profiling","pmids":["16410041"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"H2A.Z colocalizes with histone modifications characteristic of transcriptionally permissive euchromatin (H3K4me3) but not heterochromatin markers. H2A.Z is enriched at transcription start sites (TSS) of both active and silent stage-specific genes, but at var gene promoters H2A.Z enrichment at the TSS occurs only during active transcription in ring stage, indicating that temporal var gene regulation involves histone variant exchange at promoter nucleosomes. PfSir2A antagonizes H2A.Z occupancy at active var promoters during intraerythrocytic development.","method":"ChIP-seq, ChIP (co-precipitating H3K4me3 with H2A.Z antibodies), Sir2A/Sir2B knockout parasite analysis","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal ChIP, genetic knockouts (Sir2A/Sir2B), genome-wide occupancy, multiple orthogonal methods in a single study","pmids":["21379342"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Within nucleosomes, H2A.Z dimerizes with the apicomplexan-specific histone variant H2B.Z, forming double-variant nucleosomes. These H2A.Z/H2B.Z double-variant nucleosomes are enriched in intergenic (promoter) regions across the genome and carry euchromatin markers (H3K4me3 and histone acetylation). At var genes, H2A.Z/H2B.Z double-variant nucleosomes are enriched only at the promoter of the single active var copy in a developmentally regulated manner.","method":"ChIP-seq, co-immunoprecipitation (demonstrating H2A.Z–H2B.Z dimerization within nucleosomes)","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP demonstrating physical dimerization, genome-wide ChIP-seq, replicated by independent lab (PMID:23320541)","pmids":["23373537","23320541"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"H2A.Z and H2B.Z together form a double-variant nucleosome subtype that localizes to euchromatic intergenic (promoter) regions throughout intraerythrocytic development. H2A.Z/H2B.Z occupancy is enriched in promoters over 3' intergenic regions and generally correlates with promoter strength but not with its temporal activity. H2B.Z occupancy exhibits a clear correlation with the AT content of the underlying DNA sequence.","method":"ChIP-seq genome-wide analysis, co-localization analysis","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide ChIP-seq with multiple orthogonal marks, independently replicated (PMID:23373537)","pmids":["23320541"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"H2A.Z is present within centromeric regions (4–4.5 kb) of all P. falciparum chromosomes that are occupied by the centromeric histone PfCENH3, indicating that H2A.Z co-occupies centromeric chromatin alongside PfCENH3.","method":"ChIP-seq mapping of PfCENH3 and H2A.Z genome-wide","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq co-localization in a single study; centromere co-occupancy is a direct finding but mechanistic consequence not fully established","pmids":["22507744"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"H2A.Z colocalizes with H3K18ac and H3K27ac at regulatory sites upstream of genes and co-localizes with transcription factor PfAP2-I and bromodomain protein PfBDP1 at stably positioned nucleosomes within regions of exposed DNA at active transcriptional start sites in schizont stages. Sequences enriched with colocalized H3K18ac, H3K27ac, and H2A.Z possess promoter activity in schizont stages but no enhancer-like activity, as demonstrated by transient transfection assays.","method":"ChIP-seq, transient transfection promoter assays, integration with existing ChIP-seq datasets","journal":"Epigenetics & chromatin","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq plus functional transfection assay, single lab, multiple orthogonal methods","pmids":["33225957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PfArp4, an actin-related protein, co-localizes with H2A.Z and the euchromatic marker H3K9ac in intergenic regions. Inducible knockdown of PfArp4 results in depletion of H2A.Z and reduced H3K9ac levels at upstream regions of euchromatic genes, repressing the transcriptional abundance of H2A.Z-dependent genes. This implicates PfArp4 as a regulator of H2A.Z deposition.","method":"Conditional glmS ribozyme knockdown, ChIP-seq, RNA-seq, co-IFA, co-IP","journal":"Parasites & vectors","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with ChIP-seq and RNA-seq demonstrating loss of H2A.Z deposition, single lab","pmids":["32552779"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"The PfBDP1 bromodomain interacts with multi-acetylated H2A.Z (detected by solution NMR spectroscopy and ITC binding assays), though this interaction is weaker than with tetra-acetylated H4 or acetylated H3.","method":"Solution NMR spectroscopy, isothermal titration calorimetry (ITC), crystal structure of PfBDP1 bromodomain","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro binding assay (NMR + ITC) with structural validation, but single lab and the H2A.Z interaction is described as weaker/secondary","pmids":["36328269"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfSir2 histone deacetylases antagonize acetylated H2A.Z at boundaries between active and silent DNA. Acetylation of H2A.Z at promoters is dynamically associated with promoter activity across the genome, implicating acetylation of H2A.Z in genome-wide gene regulation.","method":"ChIP-seq with Sir2 knockout/knockdown parasites, genome-wide mapping of acetylated alternative histones","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq in genetic mutants (Sir2 knockouts), single lab; corroborates earlier Sir2A antagonism finding (PMID:21379342)","pmids":["37882786"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"In female gametocytes, H2A.Z and H2B.Z are highly enriched in H3K9me3-associated heterochromatin, representing a sex-specific chromatin state distinct from asexual parasites where H2A.Z/H2B.Z are euchromatic.","method":"ChIP-seq after flow-cytometry separation of male and female gametocytes, RNAseq","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq in sorted cell populations, single lab, novel finding in a distinct life stage","pmids":["37013531"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"H2A.Z and H2B.Z were found associated with the PfSWR1 complex by reciprocal pulldown experiments, indicating that the PfSWR1 chromatin remodeling complex is responsible for the deposition of the H2A.Z/H2B.Z variant histone pair at activated promoters.","method":"Reciprocal co-immunoprecipitation/pulldown (using PfEAF2 as bait), mass spectrometry identification of complex components","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal pulldown identifying H2A.Z association with PfSWR1, single lab, single study","pmids":["38564734"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"PfH2A.Z modulates PfHP1 phase separation in vitro; specifically, PfH2A.Z tunes the phase separation behavior of PfHP1 (P. falciparum heterochromatin protein 1), which compartmentalizes DNA and mediates var gene silencing.","method":"In vitro phase separation assays, single-molecule DNA compaction assays, Hi-C, FRAP of GFP-PfHP1 parasites, point mutagenesis of PfHP1","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro reconstitution assay demonstrating H2A.Z modulation of PfHP1 phase separation; single lab, single study; H2A.Z is a modulator in this assay but the primary subject of the paper is PfHP1","pmids":["41871101"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, H2A.Z is a constitutive feature of euchromatic intergenic/promoter regions that forms double-variant nucleosomes by dimerizing with the apicomplexan-specific variant H2B.Z; these nucleosomes carry active marks (H3K9ac, H3K4me3, H3K18ac, H3K27ac) and are deposited by the PfSWR1 complex (regulated by PfArp4), while their acetylation is antagonized by PfSir2 deacetylases at heterochromatin boundaries; H2A.Z occupancy at var gene promoters is dynamically regulated during the intraerythrocytic cycle to control mutually exclusive var gene expression, H2A.Z is also present at centromeres, its acetylated form is recognized by the PfBDP1 bromodomain, and in female gametocytes it unusually associates with heterochromatin, collectively placing H2A.Z as a central scaffold for epigenetic regulation of gene expression and genome organization throughout the parasite life cycle."},"narrative":{"mechanistic_narrative":"In Plasmodium falciparum, H2A.Z is a variant histone that serves as a constitutive scaffold marking euchromatic intergenic and promoter regions throughout the intraerythrocytic cycle, where it almost perfectly colocalizes with the active marks H3K9ac and H3K4me3 and provides a platform for assembly of transcription-related complexes [PMID:21187892, PMID:21379342]. Within these nucleosomes H2A.Z dimerizes with the apicomplexan-specific variant H2B.Z to form double-variant nucleosomes that carry euchromatic acetylation and H3K4me3 and are enriched at promoters, with occupancy correlating with promoter strength [PMID:23373537, PMID:23320541]. Deposition of the H2A.Z/H2B.Z pair at activated promoters is carried out by the PfSWR1 chromatin remodeling complex, and PfArp4 is required for H2A.Z deposition and the associated H3K9ac at euchromatic gene upstream regions [PMID:38564734, PMID:32552779]. The acetylation state of H2A.Z is dynamically linked to promoter activity genome-wide and is antagonized by PfSir2 deacetylases at boundaries between active and silent chromatin [PMID:37882786, PMID:21379342], and its multi-acetylated form is recognized by the PfBDP1 bromodomain [PMID:36328269, PMID:33225957]. At var gene promoters, H2A.Z/H2B.Z enrichment at the transcription start site occurs specifically at the single active copy in a developmentally regulated manner, linking histone variant exchange to mutually exclusive var gene expression [PMID:21379342, PMID:23373537, PMID:23320541]. Beyond euchromatin, H2A.Z co-occupies centromeric chromatin alongside PfCENH3 [PMID:22507744], modulates PfHP1 phase separation in vitro [PMID:41871101], and in female gametocytes adopts an unusual heterochromatic state enriched in H3K9me3-associated regions [PMID:37013531].","teleology":[{"year":2006,"claim":"Establishing that P. falciparum encodes and expresses H2A.Z with a distinctive PTM pattern was the first step in defining it as a functional variant histone distinct from canonical histones.","evidence":"Mass spectrometry, RT-PCR, and immunoblotting mapping H2A.Z modifications and stage-specific expression","pmids":["16410041"],"confidence":"Medium","gaps":["Functional consequence of the identified lysine modifications not determined","No genome-wide localization at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Genome-wide mapping resolved where H2A.Z acts, showing it constitutively marks euchromatic intergenic regions and colocalizes with active histone marks, establishing it as a stable epigenetic platform rather than a dynamic mark itself.","evidence":"ChIP-seq across intraerythrocytic development combined with RNA-seq at eight time-points","pmids":["21187892"],"confidence":"High","gaps":["Whether H2A.Z deposition is cause or consequence of active marks not resolved","Depositing machinery not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Correlating H2A.Z occupancy with var gene activity connected histone variant exchange to mutually exclusive var expression and identified PfSir2A as an antagonist, linking a chromatin variant to antigenic variation.","evidence":"ChIP-seq, reciprocal ChIP with H3K4me3, and Sir2A/Sir2B knockout analysis","pmids":["21379342"],"confidence":"High","gaps":["Mechanism of stage-specific H2A.Z exchange at var promoters not defined","Direct role in switching versus maintenance not distinguished"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Mapping H2A.Z within PfCENH3-occupied centromeres extended its role beyond gene regulation into genome organization.","evidence":"ChIP-seq co-localization of H2A.Z and PfCENH3 across all chromosomes","pmids":["22507744"],"confidence":"Medium","gaps":["Mechanistic consequence of centromeric H2A.Z not established","Whether H2A.Z contributes to kinetochore function unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Demonstrating that H2A.Z physically dimerizes with the apicomplexan-specific H2B.Z defined a novel double-variant nucleosome as the functional unit marking euchromatic promoters.","evidence":"Co-immunoprecipitation showing H2A.Z–H2B.Z dimerization plus genome-wide ChIP-seq, independently replicated across two studies","pmids":["23373537","23320541"],"confidence":"High","gaps":["Structural basis of the double-variant nucleosome not resolved","Why occupancy correlates with promoter strength but not temporal activity unexplained"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Integrating H2A.Z with additional acetyl marks, PfAP2-I, and PfBDP1, and testing regulatory activity, positioned H2A.Z-marked sites as functional promoters read by defined factors.","evidence":"ChIP-seq colocalization with H3K18ac/H3K27ac, PfAP2-I and PfBDP1, plus transient transfection promoter assays","pmids":["33225957"],"confidence":"Medium","gaps":["Distinction from enhancer function not fully explained","Causal requirement of H2A.Z for reader recruitment not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Conditional depletion of PfArp4 identified an upstream regulator required for H2A.Z deposition, providing the first genetic handle on the machinery that places H2A.Z.","evidence":"glmS ribozyme knockdown with ChIP-seq, RNA-seq, co-IFA and co-IP","pmids":["32552779"],"confidence":"Medium","gaps":["Whether PfArp4 acts directly or via a remodeler complex not resolved at the time","Full deposition complex composition unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"In vitro binding assays established that multi-acetylated H2A.Z is directly recognized by the PfBDP1 bromodomain, defining a molecular reader interaction.","evidence":"Solution NMR and ITC binding assays with the PfBDP1 bromodomain crystal structure","pmids":["36328269"],"confidence":"Medium","gaps":["Interaction weaker than with acetylated H4/H3, cellular relevance not quantified","Functional outcome of PfBDP1–H2A.Z binding in vivo not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Genome-wide mapping in Sir2 mutants showed H2A.Z acetylation tracks promoter activity and is antagonized by PfSir2 at active/silent boundaries, establishing acetylation of the variant as a regulatory switch.","evidence":"ChIP-seq in Sir2 knockout/knockdown parasites mapping acetylated alternative histones","pmids":["37882786"],"confidence":"Medium","gaps":["Direct enzyme–substrate relationship of PfSir2 on H2A.Z not shown biochemically","Acetyltransferase responsible not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Discovering that H2A.Z/H2B.Z become heterochromatic in female gametocytes revealed a life-stage- and sex-specific reprogramming of the variant's chromatin context.","evidence":"ChIP-seq and RNA-seq on flow-sorted male and female gametocytes","pmids":["37013531"],"confidence":"Medium","gaps":["Mechanism driving the euchromatin-to-heterochromatin switch unknown","Functional consequence for gametocyte gene expression not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Reciprocal pulldowns identified the PfSWR1 complex as the machinery associating with and depositing the H2A.Z/H2B.Z pair at activated promoters, completing the deposition pathway.","evidence":"Reciprocal co-IP/pulldown using PfEAF2 as bait with mass spectrometry of complex components","pmids":["38564734"],"confidence":"Medium","gaps":["In vitro reconstitution of PfSWR1-mediated H2A.Z deposition not shown","How PfSWR1 is targeted to specific promoters not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"In vitro reconstitution showed H2A.Z modulates PfHP1 phase separation, linking the variant to heterochromatin compartmentalization and var gene silencing beyond its euchromatic role.","evidence":"In vitro phase separation and single-molecule DNA compaction assays, Hi-C, FRAP of GFP-PfHP1, and PfHP1 point mutagenesis","pmids":["41871101"],"confidence":"Medium","gaps":["Effect demonstrated in vitro; in vivo requirement of H2A.Z for PfHP1 condensation not established","H2A.Z is a modulator, not the primary subject, in this assay"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How H2A.Z occupancy and acetylation are dynamically read out to enforce a single active var gene, and how the same variant is redirected to heterochromatin in female gametocytes, remain the central open mechanistic questions.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the P. falciparum H2A.Z/H2B.Z nucleosome","Direct causal test of H2A.Z removal on var switching lacking","Signals controlling stage- and sex-specific chromatin context of H2A.Z unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["H2A.Z/H2B.Z double-variant nucleosome","PfSWR1 chromatin remodeling complex (association)"],"partners":["H2B.Z (DIMERIZATION PARTNER)","PFSWR1 / PFEAF2 (DEPOSITION COMPLEX)","PFARP4 (DEPOSITION REGULATOR)","PFSIR2 / PFSIR2A (DEACETYLASE ANTAGONIST)","PFBDP1 BROMODOMAIN (READER OF ACETYLATED H2A.Z)","PFAP2-I (CO-LOCALIZING TRANSCRIPTION FACTOR)","PFCENH3 (CENTROMERIC CO-OCCUPANCY)","PFHP1 (PHASE SEPARATION MODULATION)"],"other_free_text":["Constitutively marks euchromatic intergenic/promoter regions and colocalizes with H3K9ac, H3K4me3, H3K18ac, H3K27ac.","H2A.Z acetylation state dynamically tracks promoter activity genome-wide.","At var promoters, H2A.Z/H2B.Z enrichment at the TSS is restricted to the single active copy in a developmentally regulated manner, linking it to mutually exclusive var expression.","Displays a sex-specific chromatin state: euchromatic in asexual stages but heterochromatic (H3K9me3-associated) in female gametocytes."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"21187892","id":"PMC_21187892","title":"H2A.Z demarcates intergenic regions of the plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3.","date":"2010","source":"PLoS 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chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40049416","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["H2A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41871101","id":"PMC_41871101","title":"Phase separation of heterochromatin protein 1 regulates virulence gene expression in Plasmodium falciparum.","date":"2026","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/41871101","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfH2A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12543,"output_tokens":3810,"usd":0.04739,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9775,"output_tokens":4879,"usd":0.085425,"stage2_stop_reason":"end_turn"},"total_usd":0.132815,"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\": 2010,\n      \"finding\": \"H2A.Z is a constant, ubiquitous feature of euchromatic intergenic regions throughout the intraerythrocytic cycle in P. falciparum, and almost perfectly colocalizes with H3K9ac and H3K4me3, suggesting these marks are preferentially deposited on H2A.Z-containing nucleosomes. H2A.Z stably defines intergenic regions and provides a platform for dynamic assembly of epigenetic and transcription-related complexes.\",\n      \"method\": \"Genome-wide ChIP-seq (next-generation sequencing with linear amplification method) across intraerythrocytic development, combined with RNA-seq at 8 time-points\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide ChIP-seq with multiple orthogonal marks (H3K9ac, H3K4me3) and RNA-seq, providing comprehensive mechanistic placement of H2A.Z in the P. falciparum epigenome\",\n      \"pmids\": [\"21187892\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Mass spectrometry identified a novel pattern of lysine modifications on H2A.Z in P. falciparum. The variant histone H2A.Z is encoded in the P. falciparum genome and its expression decreases in mid- or late trophozoite stages, in contrast to canonical histones which peak at late trophozoite.\",\n      \"method\": \"Mass spectrometry, real-time RT-PCR, immunoblotting\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry and immunoblotting in a single study providing direct PTM identification and expression profiling\",\n      \"pmids\": [\"16410041\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"H2A.Z colocalizes with histone modifications characteristic of transcriptionally permissive euchromatin (H3K4me3) but not heterochromatin markers. H2A.Z is enriched at transcription start sites (TSS) of both active and silent stage-specific genes, but at var gene promoters H2A.Z enrichment at the TSS occurs only during active transcription in ring stage, indicating that temporal var gene regulation involves histone variant exchange at promoter nucleosomes. PfSir2A antagonizes H2A.Z occupancy at active var promoters during intraerythrocytic development.\",\n      \"method\": \"ChIP-seq, ChIP (co-precipitating H3K4me3 with H2A.Z antibodies), Sir2A/Sir2B knockout parasite analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal ChIP, genetic knockouts (Sir2A/Sir2B), genome-wide occupancy, multiple orthogonal methods in a single study\",\n      \"pmids\": [\"21379342\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Within nucleosomes, H2A.Z dimerizes with the apicomplexan-specific histone variant H2B.Z, forming double-variant nucleosomes. These H2A.Z/H2B.Z double-variant nucleosomes are enriched in intergenic (promoter) regions across the genome and carry euchromatin markers (H3K4me3 and histone acetylation). At var genes, H2A.Z/H2B.Z double-variant nucleosomes are enriched only at the promoter of the single active var copy in a developmentally regulated manner.\",\n      \"method\": \"ChIP-seq, co-immunoprecipitation (demonstrating H2A.Z–H2B.Z dimerization within nucleosomes)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP demonstrating physical dimerization, genome-wide ChIP-seq, replicated by independent lab (PMID:23320541)\",\n      \"pmids\": [\"23373537\", \"23320541\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"H2A.Z and H2B.Z together form a double-variant nucleosome subtype that localizes to euchromatic intergenic (promoter) regions throughout intraerythrocytic development. H2A.Z/H2B.Z occupancy is enriched in promoters over 3' intergenic regions and generally correlates with promoter strength but not with its temporal activity. H2B.Z occupancy exhibits a clear correlation with the AT content of the underlying DNA sequence.\",\n      \"method\": \"ChIP-seq genome-wide analysis, co-localization analysis\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide ChIP-seq with multiple orthogonal marks, independently replicated (PMID:23373537)\",\n      \"pmids\": [\"23320541\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"H2A.Z is present within centromeric regions (4–4.5 kb) of all P. falciparum chromosomes that are occupied by the centromeric histone PfCENH3, indicating that H2A.Z co-occupies centromeric chromatin alongside PfCENH3.\",\n      \"method\": \"ChIP-seq mapping of PfCENH3 and H2A.Z genome-wide\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq co-localization in a single study; centromere co-occupancy is a direct finding but mechanistic consequence not fully established\",\n      \"pmids\": [\"22507744\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"H2A.Z colocalizes with H3K18ac and H3K27ac at regulatory sites upstream of genes and co-localizes with transcription factor PfAP2-I and bromodomain protein PfBDP1 at stably positioned nucleosomes within regions of exposed DNA at active transcriptional start sites in schizont stages. Sequences enriched with colocalized H3K18ac, H3K27ac, and H2A.Z possess promoter activity in schizont stages but no enhancer-like activity, as demonstrated by transient transfection assays.\",\n      \"method\": \"ChIP-seq, transient transfection promoter assays, integration with existing ChIP-seq datasets\",\n      \"journal\": \"Epigenetics & chromatin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq plus functional transfection assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"33225957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PfArp4, an actin-related protein, co-localizes with H2A.Z and the euchromatic marker H3K9ac in intergenic regions. Inducible knockdown of PfArp4 results in depletion of H2A.Z and reduced H3K9ac levels at upstream regions of euchromatic genes, repressing the transcriptional abundance of H2A.Z-dependent genes. This implicates PfArp4 as a regulator of H2A.Z deposition.\",\n      \"method\": \"Conditional glmS ribozyme knockdown, ChIP-seq, RNA-seq, co-IFA, co-IP\",\n      \"journal\": \"Parasites & vectors\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with ChIP-seq and RNA-seq demonstrating loss of H2A.Z deposition, single lab\",\n      \"pmids\": [\"32552779\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The PfBDP1 bromodomain interacts with multi-acetylated H2A.Z (detected by solution NMR spectroscopy and ITC binding assays), though this interaction is weaker than with tetra-acetylated H4 or acetylated H3.\",\n      \"method\": \"Solution NMR spectroscopy, isothermal titration calorimetry (ITC), crystal structure of PfBDP1 bromodomain\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro binding assay (NMR + ITC) with structural validation, but single lab and the H2A.Z interaction is described as weaker/secondary\",\n      \"pmids\": [\"36328269\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfSir2 histone deacetylases antagonize acetylated H2A.Z at boundaries between active and silent DNA. Acetylation of H2A.Z at promoters is dynamically associated with promoter activity across the genome, implicating acetylation of H2A.Z in genome-wide gene regulation.\",\n      \"method\": \"ChIP-seq with Sir2 knockout/knockdown parasites, genome-wide mapping of acetylated alternative histones\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq in genetic mutants (Sir2 knockouts), single lab; corroborates earlier Sir2A antagonism finding (PMID:21379342)\",\n      \"pmids\": [\"37882786\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In female gametocytes, H2A.Z and H2B.Z are highly enriched in H3K9me3-associated heterochromatin, representing a sex-specific chromatin state distinct from asexual parasites where H2A.Z/H2B.Z are euchromatic.\",\n      \"method\": \"ChIP-seq after flow-cytometry separation of male and female gametocytes, RNAseq\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq in sorted cell populations, single lab, novel finding in a distinct life stage\",\n      \"pmids\": [\"37013531\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"H2A.Z and H2B.Z were found associated with the PfSWR1 complex by reciprocal pulldown experiments, indicating that the PfSWR1 chromatin remodeling complex is responsible for the deposition of the H2A.Z/H2B.Z variant histone pair at activated promoters.\",\n      \"method\": \"Reciprocal co-immunoprecipitation/pulldown (using PfEAF2 as bait), mass spectrometry identification of complex components\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pulldown identifying H2A.Z association with PfSWR1, single lab, single study\",\n      \"pmids\": [\"38564734\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"PfH2A.Z modulates PfHP1 phase separation in vitro; specifically, PfH2A.Z tunes the phase separation behavior of PfHP1 (P. falciparum heterochromatin protein 1), which compartmentalizes DNA and mediates var gene silencing.\",\n      \"method\": \"In vitro phase separation assays, single-molecule DNA compaction assays, Hi-C, FRAP of GFP-PfHP1 parasites, point mutagenesis of PfHP1\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro reconstitution assay demonstrating H2A.Z modulation of PfHP1 phase separation; single lab, single study; H2A.Z is a modulator in this assay but the primary subject of the paper is PfHP1\",\n      \"pmids\": [\"41871101\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, H2A.Z is a constitutive feature of euchromatic intergenic/promoter regions that forms double-variant nucleosomes by dimerizing with the apicomplexan-specific variant H2B.Z; these nucleosomes carry active marks (H3K9ac, H3K4me3, H3K18ac, H3K27ac) and are deposited by the PfSWR1 complex (regulated by PfArp4), while their acetylation is antagonized by PfSir2 deacetylases at heterochromatin boundaries; H2A.Z occupancy at var gene promoters is dynamically regulated during the intraerythrocytic cycle to control mutually exclusive var gene expression, H2A.Z is also present at centromeres, its acetylated form is recognized by the PfBDP1 bromodomain, and in female gametocytes it unusually associates with heterochromatin, collectively placing H2A.Z as a central scaffold for epigenetic regulation of gene expression and genome organization throughout the parasite life cycle.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In Plasmodium falciparum, H2A.Z is a variant histone that serves as a constitutive scaffold marking euchromatic intergenic and promoter regions throughout the intraerythrocytic cycle, where it almost perfectly colocalizes with the active marks H3K9ac and H3K4me3 and provides a platform for assembly of transcription-related complexes [#0, #2]. Within these nucleosomes H2A.Z dimerizes with the apicomplexan-specific variant H2B.Z to form double-variant nucleosomes that carry euchromatic acetylation and H3K4me3 and are enriched at promoters, with occupancy correlating with promoter strength [#3, #4]. Deposition of the H2A.Z/H2B.Z pair at activated promoters is carried out by the PfSWR1 chromatin remodeling complex, and PfArp4 is required for H2A.Z deposition and the associated H3K9ac at euchromatic gene upstream regions [#11, #7]. The acetylation state of H2A.Z is dynamically linked to promoter activity genome-wide and is antagonized by PfSir2 deacetylases at boundaries between active and silent chromatin [#9, #2], and its multi-acetylated form is recognized by the PfBDP1 bromodomain [#8, #6]. At var gene promoters, H2A.Z/H2B.Z enrichment at the transcription start site occurs specifically at the single active copy in a developmentally regulated manner, linking histone variant exchange to mutually exclusive var gene expression [#2, #3]. Beyond euchromatin, H2A.Z co-occupies centromeric chromatin alongside PfCENH3 [#5], modulates PfHP1 phase separation in vitro [#12], and in female gametocytes adopts an unusual heterochromatic state enriched in H3K9me3-associated regions [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that P. falciparum encodes and expresses H2A.Z with a distinctive PTM pattern was the first step in defining it as a functional variant histone distinct from canonical histones.\",\n      \"evidence\": \"Mass spectrometry, RT-PCR, and immunoblotting mapping H2A.Z modifications and stage-specific expression\",\n      \"pmids\": [\"16410041\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the identified lysine modifications not determined\", \"No genome-wide localization at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Genome-wide mapping resolved where H2A.Z acts, showing it constitutively marks euchromatic intergenic regions and colocalizes with active histone marks, establishing it as a stable epigenetic platform rather than a dynamic mark itself.\",\n      \"evidence\": \"ChIP-seq across intraerythrocytic development combined with RNA-seq at eight time-points\",\n      \"pmids\": [\"21187892\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether H2A.Z deposition is cause or consequence of active marks not resolved\", \"Depositing machinery not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Correlating H2A.Z occupancy with var gene activity connected histone variant exchange to mutually exclusive var expression and identified PfSir2A as an antagonist, linking a chromatin variant to antigenic variation.\",\n      \"evidence\": \"ChIP-seq, reciprocal ChIP with H3K4me3, and Sir2A/Sir2B knockout analysis\",\n      \"pmids\": [\"21379342\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of stage-specific H2A.Z exchange at var promoters not defined\", \"Direct role in switching versus maintenance not distinguished\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Mapping H2A.Z within PfCENH3-occupied centromeres extended its role beyond gene regulation into genome organization.\",\n      \"evidence\": \"ChIP-seq co-localization of H2A.Z and PfCENH3 across all chromosomes\",\n      \"pmids\": [\"22507744\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic consequence of centromeric H2A.Z not established\", \"Whether H2A.Z contributes to kinetochore function unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrating that H2A.Z physically dimerizes with the apicomplexan-specific H2B.Z defined a novel double-variant nucleosome as the functional unit marking euchromatic promoters.\",\n      \"evidence\": \"Co-immunoprecipitation showing H2A.Z–H2B.Z dimerization plus genome-wide ChIP-seq, independently replicated across two studies\",\n      \"pmids\": [\"23373537\", \"23320541\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the double-variant nucleosome not resolved\", \"Why occupancy correlates with promoter strength but not temporal activity unexplained\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Integrating H2A.Z with additional acetyl marks, PfAP2-I, and PfBDP1, and testing regulatory activity, positioned H2A.Z-marked sites as functional promoters read by defined factors.\",\n      \"evidence\": \"ChIP-seq colocalization with H3K18ac/H3K27ac, PfAP2-I and PfBDP1, plus transient transfection promoter assays\",\n      \"pmids\": [\"33225957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Distinction from enhancer function not fully explained\", \"Causal requirement of H2A.Z for reader recruitment not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Conditional depletion of PfArp4 identified an upstream regulator required for H2A.Z deposition, providing the first genetic handle on the machinery that places H2A.Z.\",\n      \"evidence\": \"glmS ribozyme knockdown with ChIP-seq, RNA-seq, co-IFA and co-IP\",\n      \"pmids\": [\"32552779\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether PfArp4 acts directly or via a remodeler complex not resolved at the time\", \"Full deposition complex composition unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"In vitro binding assays established that multi-acetylated H2A.Z is directly recognized by the PfBDP1 bromodomain, defining a molecular reader interaction.\",\n      \"evidence\": \"Solution NMR and ITC binding assays with the PfBDP1 bromodomain crystal structure\",\n      \"pmids\": [\"36328269\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction weaker than with acetylated H4/H3, cellular relevance not quantified\", \"Functional outcome of PfBDP1–H2A.Z binding in vivo not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Genome-wide mapping in Sir2 mutants showed H2A.Z acetylation tracks promoter activity and is antagonized by PfSir2 at active/silent boundaries, establishing acetylation of the variant as a regulatory switch.\",\n      \"evidence\": \"ChIP-seq in Sir2 knockout/knockdown parasites mapping acetylated alternative histones\",\n      \"pmids\": [\"37882786\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct enzyme–substrate relationship of PfSir2 on H2A.Z not shown biochemically\", \"Acetyltransferase responsible not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Discovering that H2A.Z/H2B.Z become heterochromatic in female gametocytes revealed a life-stage- and sex-specific reprogramming of the variant's chromatin context.\",\n      \"evidence\": \"ChIP-seq and RNA-seq on flow-sorted male and female gametocytes\",\n      \"pmids\": [\"37013531\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism driving the euchromatin-to-heterochromatin switch unknown\", \"Functional consequence for gametocyte gene expression not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Reciprocal pulldowns identified the PfSWR1 complex as the machinery associating with and depositing the H2A.Z/H2B.Z pair at activated promoters, completing the deposition pathway.\",\n      \"evidence\": \"Reciprocal co-IP/pulldown using PfEAF2 as bait with mass spectrometry of complex components\",\n      \"pmids\": [\"38564734\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vitro reconstitution of PfSWR1-mediated H2A.Z deposition not shown\", \"How PfSWR1 is targeted to specific promoters not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"In vitro reconstitution showed H2A.Z modulates PfHP1 phase separation, linking the variant to heterochromatin compartmentalization and var gene silencing beyond its euchromatic role.\",\n      \"evidence\": \"In vitro phase separation and single-molecule DNA compaction assays, Hi-C, FRAP of GFP-PfHP1, and PfHP1 point mutagenesis\",\n      \"pmids\": [\"41871101\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Effect demonstrated in vitro; in vivo requirement of H2A.Z for PfHP1 condensation not established\", \"H2A.Z is a modulator, not the primary subject, in this assay\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How H2A.Z occupancy and acetylation are dynamically read out to enforce a single active var gene, and how the same variant is redirected to heterochromatin in female gametocytes, remain the central open mechanistic questions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the P. falciparum H2A.Z/H2B.Z nucleosome\", \"Direct causal test of H2A.Z removal on var switching lacking\", \"Signals controlling stage- and sex-specific chromatin context of H2A.Z unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0031492\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0046982\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0003682\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000786\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0000775\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006357\", \"supporting_discovery_ids\": [0, 2, 6, 9]},\n      {\"term_id\": \"GO:0006338\", \"supporting_discovery_ids\": [7, 11]},\n      {\"term_id\": \"GO:0045814\", \"supporting_discovery_ids\": [2, 12]}\n    ],\n    \"complexes\": [\n      \"H2A.Z/H2B.Z double-variant nucleosome\",\n      \"PfSWR1 chromatin remodeling complex (association)\"\n    ],\n    \"partners\": [\n      \"H2B.Z (dimerization partner)\",\n      \"PfSWR1 / PfEAF2 (deposition complex)\",\n      \"PfArp4 (deposition regulator)\",\n      \"PfSir2 / PfSir2A (deacetylase antagonist)\",\n      \"PfBDP1 bromodomain (reader of acetylated H2A.Z)\",\n      \"PfAP2-I (co-localizing transcription factor)\",\n      \"PfCENH3 (centromeric co-occupancy)\",\n      \"PfHP1 (phase separation modulation)\"\n    ],\n    \"other_free_text\": [\n      \"Constitutively marks euchromatic intergenic/promoter regions and colocalizes with H3K9ac, H3K4me3, H3K18ac, H3K27ac.\",\n      \"H2A.Z acetylation state dynamically tracks promoter activity genome-wide.\",\n      \"At var promoters, H2A.Z/H2B.Z enrichment at the TSS is restricted to the single active copy in a developmentally regulated manner, linking it to mutually exclusive var expression.\",\n      \"Displays a sex-specific chromatin state: euchromatic in asexual stages but heterochromatic (H3K9me3-associated) in female gametocytes.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0320900","name":null,"product":"histone H2A.Z","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1217600","name":null,"product":"histone H2A.Z, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}