{"gene":"ZNHIT1","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":2007,"finding":"ZNHIT1/p18(Hamlet) is a substrate of p38 MAPK that becomes stabilized and accumulates in response to genotoxic stresses (UV, cisplatin). It physically interacts with p53 and stimulates transcription of proapoptotic p53 target genes PUMA and NOXA by enhancing p53 recruitment to their promoters, thereby inducing apoptosis. Low steady-state levels are maintained by a p53-dependent negative feedback loop in proliferating cells.","method":"Protein overexpression and knockdown with apoptosis readouts; co-immunoprecipitation of p18(Hamlet) with p53; chromatin immunoprecipitation (ChIP) showing p53 recruitment to PUMA/NOXA promoters; p38 MAPK inhibitor and substrate assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction (Co-IP with p53), ChIP for promoter recruitment, loss-of-function and gain-of-function experiments, multiple orthogonal methods in a single focused study","pmids":["17380123"],"is_preprint":false},{"year":2007,"finding":"In addition to apoptosis (via PUMA/NOXA), ZNHIT1/p18(Hamlet) can also mediate p53-dependent cell cycle arrest in response to gamma-irradiation by participating in the upregulation of the cell cycle inhibitor p21(Cip1)/CDKN1A.","method":"Knockdown of p18(Hamlet) in gamma-irradiated cells with cell cycle and p21 expression readouts; ChIP for p53 binding at p21 promoter","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single paper extending prior findings, loss-of-function with specific transcriptional readout but limited orthogonal methods reported in abstract","pmids":["17700068"],"is_preprint":false},{"year":2010,"finding":"ZNHIT1/p18(Hamlet) functions as a subunit of the SRCAP chromatin-remodeling complex. In a p38 MAPK-dependent manner, it is recruited to the myogenin promoter at the onset of muscle differentiation and is required for H2A.Z incorporation at this locus, leading to transcriptional activation of muscle differentiation genes.","method":"ChIP showing p18(Hamlet) and H2A.Z recruitment to myogenin promoter; siRNA knockdown of SRCAP subunits with muscle gene expression readouts; p38 MAPK inhibitor experiments linking pathway to chromatin remodeling","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — ChIP for both subunit recruitment and histone variant incorporation, loss-of-function with specific transcriptional and differentiation phenotype, multiple SRCAP subunit knockdowns, p38 MAPK pathway placement","pmids":["20473270"],"is_preprint":false},{"year":2012,"finding":"The Drosophila homolog of ZNHIT1/p18(Hamlet) (Dmp18), a subunit of the SWR1/SRCAP chromatin-remodeling complex, physically interacts with the Dmp52 subunit of TFIIH and co-localizes with TFIIH in chromatin. Genetic interaction between Dmp18 and the TFIIH subunit Dmp8 suggests functional cross-talk between the SWR1/SRCAP complex and TFIIH.","method":"Co-immunoprecipitation (Dmp18 with Dmp52/TFIIH); co-localization by immunofluorescence on chromatin; Drosophila genetic interaction assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus genetic epistasis in Drosophila ortholog, two orthogonal methods, single lab","pmids":["22865882"],"is_preprint":false}],"current_model":"ZNHIT1/p18(Hamlet) is a p38 MAPK substrate and subunit of the SRCAP chromatin-remodeling complex that, upon genotoxic stress, is stabilized and physically interacts with p53 to enhance transcription of proapoptotic genes (PUMA, NOXA) or the cell cycle inhibitor p21, and during muscle differentiation is recruited in a p38 MAPK-dependent manner to gene promoters where it drives H2A.Z histone incorporation and transcriptional activation; its Drosophila homolog also physically associates with the TFIIH complex, suggesting an additional interface with DNA repair/transcription machinery."},"narrative":{"mechanistic_narrative":"ZNHIT1/p18(Hamlet) is a chromatin-associated regulator that couples p38 MAPK signaling to transcriptional programs governing stress responses and cell differentiation [PMID:17380123, PMID:20473270]. As a substrate of p38 MAPK, it is stabilized and accumulates upon genotoxic stress (UV, cisplatin), where it physically interacts with p53 and enhances p53 recruitment to target promoters to drive transcription of the proapoptotic genes PUMA and NOXA, inducing apoptosis; its steady-state levels are restrained in proliferating cells by a p53-dependent negative feedback loop [PMID:17380123]. The same factor also participates in p53-dependent cell cycle arrest after gamma-irradiation through upregulation of the CDK inhibitor p21/CDKN1A [PMID:17700068]. Independently of its p53 role, ZNHIT1 acts as a subunit of the SRCAP chromatin-remodeling complex: in a p38 MAPK-dependent manner it is recruited to the myogenin promoter at the onset of muscle differentiation and is required for H2A.Z histone variant incorporation there, activating muscle differentiation genes [PMID:20473270]. The Drosophila homolog, also an SWR1/SRCAP subunit, physically interacts with and co-localizes with the TFIIH complex, indicating an additional interface between this remodeling complex and the transcription/repair machinery [PMID:22865882].","teleology":[{"year":2007,"claim":"Established that ZNHIT1 is a p38 MAPK substrate that links genotoxic stress signaling to p53-dependent apoptosis, answering how a stress kinase output is channeled into proapoptotic transcription.","evidence":"Overexpression/knockdown with apoptosis readouts, Co-IP of p18(Hamlet) with p53, ChIP for p53 at PUMA/NOXA promoters, and p38 inhibitor/substrate assays in mammalian cells","pmids":["17380123"],"confidence":"High","gaps":["Does not define the structural basis or domain of the p53 interaction","Mechanism by which p38 phosphorylation stabilizes the protein not resolved"]},{"year":2007,"claim":"Extended ZNHIT1's p53-axis role beyond apoptosis to cell cycle arrest, showing it also promotes p21/CDKN1A upregulation after gamma-irradiation.","evidence":"Knockdown in gamma-irradiated cells with cell cycle and p21 readouts plus ChIP for p53 at the p21 promoter","pmids":["17700068"],"confidence":"Medium","gaps":["Limited orthogonal validation in a single study","Does not explain what determines the apoptosis-versus-arrest choice"]},{"year":2010,"claim":"Identified ZNHIT1 as an SRCAP complex subunit that drives H2A.Z incorporation, defining a p53-independent chromatin-remodeling function in differentiation.","evidence":"ChIP for subunit and H2A.Z recruitment to the myogenin promoter, siRNA knockdown of SRCAP subunits, and p38 inhibitor experiments during muscle differentiation","pmids":["20473270"],"confidence":"High","gaps":["Whether the p53 and SRCAP functions are mechanistically separable not established","Genome-wide scope of H2A.Z-dependent targets not mapped"]},{"year":2012,"claim":"Demonstrated a physical and genetic link between the SWR1/SRCAP complex subunit and TFIIH in the Drosophila ortholog, indicating cross-talk with the transcription/repair machinery.","evidence":"Co-IP of Dmp18 with Dmp52/TFIIH, immunofluorescence co-localization on chromatin, and Drosophila genetic interaction assays","pmids":["22865882"],"confidence":"Medium","gaps":["Conservation of the TFIIH interaction in mammalian ZNHIT1 not shown","Functional consequence of the SRCAP-TFIIH interface undefined"]},{"year":null,"claim":"How ZNHIT1 partitions between its p53-coactivator role and its SRCAP/H2A.Z chromatin-remodeling role, and whether these converge on shared targets, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of ZNHIT1 within SRCAP or bound to p53","Genome-wide H2A.Z target map and p53 cofactor specificity not integrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[2,3]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[2,3]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[0]}],"complexes":["SRCAP chromatin-remodeling complex","SWR1 complex"],"partners":["TP53","TFIIH"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O43257","full_name":"Zinc finger HIT domain-containing protein 1","aliases":["Cyclin-G1-binding protein 1","Zinc finger protein subfamily 4A member 1","p18 Hamlet"],"length_aa":154,"mass_kda":17.5,"function":"Plays a role in chromatin remodeling by promoting the incorporation of histone variant H2AZ1/H2A.Z into the genome to regulate gene expression (PubMed:20473270, PubMed:35175558). Promotes SRCAP complex-mediated deposition of histone variant H2AZ1 to lymphoid fate regulator genes, enhancing lymphoid lineage commitment (By similarity). Recruited to the promoter of the transcriptional activator MYOG at the early stages of muscle differentiation where it mediates binding of histone H2AZ1 to chromatin and induces muscle-specific gene expression (PubMed:20473270). Maintains hematopoietic stem cell (HSC) quiescence by determining the chromatin accessibility at distal enhancers of HSC quiescence genes such as PTEN, FSTL1 and KLF4, enhancing deposition of H2AZ1 to promote their sustained transcription and restricting PI3K-AKT signaling inhibition (By similarity). Plays a role in intestinal stem cell maintenance by promoting H2AZ1 deposition at the transcription start sites of genes involved in intestinal stem cell fate determination including LGR5, TGFB1 and TGFBR2, thereby contributing to gene transcription (By similarity). Promotes phosphorylation of the H2AZ1 chaperone VPS72/YL1 which enhances the interaction between HZAZ1 and VPS72 (By similarity). Regulates the entry of male germ cells into meiosis by controlling histone H2AZ1 deposition which facilitates the expression of meiotic genes such as MEIOSIN, leading to the initiation of meiosis (By similarity). Required for postnatal heart function through its role in maintenance of cardiac Ca(2+) homeostasis by modulating the expression of Ca(2+)-regulating proteins CASQ1 and ATP2A2/SERCA2A via deposition of histone H2AZ1 at their promoters (By similarity). During embryonic heart development, required for mitochondrial maturation and oxidative metabolism by functioning through H2AZ1 deposition to activate transcription of metabolic genes and is also required to maintain the stability of the respiratory complex (By similarity). In neural cells, increases deposition of the H2AZ1 histone variant and promotes neurite growth (PubMed:35175558). Plays a role in TP53/p53-mediated apoptosis induction by stimulating the transcriptional activation of several proapoptotic p53 target genes such as PMAIP1/NOXA and BBC3/PUMA (PubMed:17380123). Mediates cell cycle arrest induced in response to gamma-irradiation by enhancing recruitment of TP53/p53 to the promoter of the cell cycle inhibitor CDKN1A, leading to its transcriptional activation (PubMed:17700068). Recruited to the promoter of cyclin-dependent kinase CDK6 and inhibits its transcription, possibly by decreasing the acetylation level of histone H4, leading to cell cycle arrest at the G1 phase (By similarity). Plays a role in lens fiber cell differentiation by regulating the expression of cell cycle regulator CDKN1A/p21Cip1 (By similarity). Binds to transcriptional repressor NR1D2 and relieves it of its inhibitory effect on the transcription of apolipoprotein APOC3 without affecting its DNA-binding activity (PubMed:17892483)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/O43257/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNHIT1","classification":"Not Classified","n_dependent_lines":355,"n_total_lines":1208,"dependency_fraction":0.29387417218543044},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"H2AFZ","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ZNHIT1","total_profiled":1310},"omim":[{"mim_id":"618617","title":"ZINC FINGER HIT DOMAIN-CONTAINING PROTEIN 1; ZNHIT1","url":"https://www.omim.org/entry/618617"},{"mim_id":"602304","title":"NUCLEAR RECEPTOR SUBFAMILY 1, GROUP D, MEMBER 2; NR1D2","url":"https://www.omim.org/entry/602304"},{"mim_id":"191170","title":"TUMOR PROTEIN p53; TP53","url":"https://www.omim.org/entry/191170"},{"mim_id":"142763","title":"H2A.Z VARIANT HISTONE 1; H2AZ1","url":"https://www.omim.org/entry/142763"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZNHIT1"},"hgnc":{"alias_symbol":["CG1I","H_DJ0747G18.14","p18(Hamlet)"],"prev_symbol":["ZNFN4A1"]},"alphafold":{"accession":"O43257","domains":[{"cath_id":"3.30.40","chopping":"114-154","consensus_level":"medium","plddt":89.3449,"start":114,"end":154}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43257","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43257-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43257-F1-predicted_aligned_error_v6.png","plddt_mean":74.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNHIT1","jax_strain_url":"https://www.jax.org/strain/search?query=ZNHIT1"},"sequence":{"accession":"O43257","fasta_url":"https://rest.uniprot.org/uniprotkb/O43257.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43257/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43257"}},"corpus_meta":[{"pmid":"17380123","id":"PMC_17380123","title":"A new p38 MAP kinase-regulated transcriptional coactivator that stimulates p53-dependent apoptosis.","date":"2007","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/17380123","citation_count":82,"is_preprint":false},{"pmid":"20473270","id":"PMC_20473270","title":"Essential role of p18Hamlet/SRCAP-mediated histone H2A.Z chromatin incorporation in muscle differentiation.","date":"2010","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/20473270","citation_count":71,"is_preprint":false},{"pmid":"17700068","id":"PMC_17700068","title":"p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents.","date":"2007","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/17700068","citation_count":18,"is_preprint":false},{"pmid":"22865882","id":"PMC_22865882","title":"Physical and functional interactions between Drosophila homologue of Swc6/p18Hamlet subunit of the SWR1/SRCAP chromatin-remodeling complex with the DNA repair/transcription factor TFIIH.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22865882","citation_count":10,"is_preprint":false},{"pmid":"30270456","id":"PMC_30270456","title":"The Dmp8-Dmp18 bicistron messenger RNA enables unusual translation during cellular stress.","date":"2018","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30270456","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4302,"output_tokens":1291,"usd":0.016136,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7956,"output_tokens":2050,"usd":0.045515,"stage2_stop_reason":"end_turn"},"total_usd":0.061651,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"ZNHIT1/p18(Hamlet) is a substrate of p38 MAPK that becomes stabilized and accumulates in response to genotoxic stresses (UV, cisplatin). It physically interacts with p53 and stimulates transcription of proapoptotic p53 target genes PUMA and NOXA by enhancing p53 recruitment to their promoters, thereby inducing apoptosis. Low steady-state levels are maintained by a p53-dependent negative feedback loop in proliferating cells.\",\n      \"method\": \"Protein overexpression and knockdown with apoptosis readouts; co-immunoprecipitation of p18(Hamlet) with p53; chromatin immunoprecipitation (ChIP) showing p53 recruitment to PUMA/NOXA promoters; p38 MAPK inhibitor and substrate assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction (Co-IP with p53), ChIP for promoter recruitment, loss-of-function and gain-of-function experiments, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"17380123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"In addition to apoptosis (via PUMA/NOXA), ZNHIT1/p18(Hamlet) can also mediate p53-dependent cell cycle arrest in response to gamma-irradiation by participating in the upregulation of the cell cycle inhibitor p21(Cip1)/CDKN1A.\",\n      \"method\": \"Knockdown of p18(Hamlet) in gamma-irradiated cells with cell cycle and p21 expression readouts; ChIP for p53 binding at p21 promoter\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single paper extending prior findings, loss-of-function with specific transcriptional readout but limited orthogonal methods reported in abstract\",\n      \"pmids\": [\"17700068\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ZNHIT1/p18(Hamlet) functions as a subunit of the SRCAP chromatin-remodeling complex. In a p38 MAPK-dependent manner, it is recruited to the myogenin promoter at the onset of muscle differentiation and is required for H2A.Z incorporation at this locus, leading to transcriptional activation of muscle differentiation genes.\",\n      \"method\": \"ChIP showing p18(Hamlet) and H2A.Z recruitment to myogenin promoter; siRNA knockdown of SRCAP subunits with muscle gene expression readouts; p38 MAPK inhibitor experiments linking pathway to chromatin remodeling\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ChIP for both subunit recruitment and histone variant incorporation, loss-of-function with specific transcriptional and differentiation phenotype, multiple SRCAP subunit knockdowns, p38 MAPK pathway placement\",\n      \"pmids\": [\"20473270\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The Drosophila homolog of ZNHIT1/p18(Hamlet) (Dmp18), a subunit of the SWR1/SRCAP chromatin-remodeling complex, physically interacts with the Dmp52 subunit of TFIIH and co-localizes with TFIIH in chromatin. Genetic interaction between Dmp18 and the TFIIH subunit Dmp8 suggests functional cross-talk between the SWR1/SRCAP complex and TFIIH.\",\n      \"method\": \"Co-immunoprecipitation (Dmp18 with Dmp52/TFIIH); co-localization by immunofluorescence on chromatin; Drosophila genetic interaction assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus genetic epistasis in Drosophila ortholog, two orthogonal methods, single lab\",\n      \"pmids\": [\"22865882\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNHIT1/p18(Hamlet) is a p38 MAPK substrate and subunit of the SRCAP chromatin-remodeling complex that, upon genotoxic stress, is stabilized and physically interacts with p53 to enhance transcription of proapoptotic genes (PUMA, NOXA) or the cell cycle inhibitor p21, and during muscle differentiation is recruited in a p38 MAPK-dependent manner to gene promoters where it drives H2A.Z histone incorporation and transcriptional activation; its Drosophila homolog also physically associates with the TFIIH complex, suggesting an additional interface with DNA repair/transcription machinery.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNHIT1/p18(Hamlet) is a chromatin-associated regulator that couples p38 MAPK signaling to transcriptional programs governing stress responses and cell differentiation [#0, #2]. As a substrate of p38 MAPK, it is stabilized and accumulates upon genotoxic stress (UV, cisplatin), where it physically interacts with p53 and enhances p53 recruitment to target promoters to drive transcription of the proapoptotic genes PUMA and NOXA, inducing apoptosis; its steady-state levels are restrained in proliferating cells by a p53-dependent negative feedback loop [#0]. The same factor also participates in p53-dependent cell cycle arrest after gamma-irradiation through upregulation of the CDK inhibitor p21/CDKN1A [#1]. Independently of its p53 role, ZNHIT1 acts as a subunit of the SRCAP chromatin-remodeling complex: in a p38 MAPK-dependent manner it is recruited to the myogenin promoter at the onset of muscle differentiation and is required for H2A.Z histone variant incorporation there, activating muscle differentiation genes [#2]. The Drosophila homolog, also an SWR1/SRCAP subunit, physically interacts with and co-localizes with the TFIIH complex, indicating an additional interface between this remodeling complex and the transcription/repair machinery [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established that ZNHIT1 is a p38 MAPK substrate that links genotoxic stress signaling to p53-dependent apoptosis, answering how a stress kinase output is channeled into proapoptotic transcription.\",\n      \"evidence\": \"Overexpression/knockdown with apoptosis readouts, Co-IP of p18(Hamlet) with p53, ChIP for p53 at PUMA/NOXA promoters, and p38 inhibitor/substrate assays in mammalian cells\",\n      \"pmids\": [\"17380123\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the structural basis or domain of the p53 interaction\", \"Mechanism by which p38 phosphorylation stabilizes the protein not resolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Extended ZNHIT1's p53-axis role beyond apoptosis to cell cycle arrest, showing it also promotes p21/CDKN1A upregulation after gamma-irradiation.\",\n      \"evidence\": \"Knockdown in gamma-irradiated cells with cell cycle and p21 readouts plus ChIP for p53 at the p21 promoter\",\n      \"pmids\": [\"17700068\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Limited orthogonal validation in a single study\", \"Does not explain what determines the apoptosis-versus-arrest choice\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified ZNHIT1 as an SRCAP complex subunit that drives H2A.Z incorporation, defining a p53-independent chromatin-remodeling function in differentiation.\",\n      \"evidence\": \"ChIP for subunit and H2A.Z recruitment to the myogenin promoter, siRNA knockdown of SRCAP subunits, and p38 inhibitor experiments during muscle differentiation\",\n      \"pmids\": [\"20473270\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the p53 and SRCAP functions are mechanistically separable not established\", \"Genome-wide scope of H2A.Z-dependent targets not mapped\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstrated a physical and genetic link between the SWR1/SRCAP complex subunit and TFIIH in the Drosophila ortholog, indicating cross-talk with the transcription/repair machinery.\",\n      \"evidence\": \"Co-IP of Dmp18 with Dmp52/TFIIH, immunofluorescence co-localization on chromatin, and Drosophila genetic interaction assays\",\n      \"pmids\": [\"22865882\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Conservation of the TFIIH interaction in mammalian ZNHIT1 not shown\", \"Functional consequence of the SRCAP-TFIIH interface undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ZNHIT1 partitions between its p53-coactivator role and its SRCAP/H2A.Z chromatin-remodeling role, and whether these converge on shared targets, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of ZNHIT1 within SRCAP or bound to p53\", \"Genome-wide H2A.Z target map and p53 cofactor specificity not integrated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"SRCAP chromatin-remodeling complex\", \"SWR1 complex\"],\n    \"partners\": [\"TP53\", \"TFIIH\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}