{"gene":"TEX10","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2015,"finding":"TEX10 was identified as a Sox2-interacting protein that is enriched at super-enhancers (SEs) in embryonic stem cells in a Sox2-dependent manner. TEX10 coordinates histone acetylation and DNA demethylation at SEs, functioning together with Tet1 and p300 to sustain pluripotency. Loss of TEX10 impairs ESC self-renewal, early embryo development, and somatic cell reprogramming.","method":"Protein interaction network analysis (Co-IP/MS), ChIP-seq, bisulfite sequencing, knockdown/knockout phenotypic assays in ESCs and reprogramming assays","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (Co-IP, ChIP-seq, DNA methylation analysis, functional KO phenotypes) in a single foundational study, replicated in human cells","pmids":["25936917"],"is_preprint":false},{"year":2017,"finding":"TEX10 interacts with Pcgf3/5 (non-canonical PRC1 components) and the transcriptional co-activator p300 in embryonic stem cells. Pcgf3/5 deletion reduces occupancy of TEX10 and p300 at target gene promoters, placing TEX10 downstream of Pcgf3/5 in a transcriptional activation complex required for mesoderm differentiation genes.","method":"Proteomic interactome (AP-MS), ChIP-seq occupancy analysis, CRISPR-Cas9 single/double knockout, RNA-seq","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal proteomic identification plus chromatin occupancy validation and genetic epistasis via CRISPR KO","pmids":["29054931"],"is_preprint":false},{"year":2020,"finding":"TEX10 promotes proliferation of colorectal cancer cells by interacting with RELA (NF-κB p65) and increasing its nuclear localization, enhancing RELA occupancy at target gene promoters and driving expression of TNFAIP8, SAT1, and IL6ST.","method":"shRNA library screen, Co-IP, ChIP, nuclear/cytoplasmic fractionation, in vitro and in vivo tumor growth assays","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP interaction plus ChIP occupancy and functional nuclear localization data, single lab","pmids":["32995120"],"is_preprint":false},{"year":2018,"finding":"TEX10 promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma through activation of the STAT3 signaling pathway, as shown by decreased stem cell marker expression and drug resistance upon TEX10 knockdown.","method":"Knockdown (shRNA/siRNA), Western blot, sphere formation assay, drug resistance assay, xenograft","journal":"Cell cycle","confidence":"Low","confidence_rationale":"Tier 3 — functional KO with pathway activation readout but no direct biochemical interaction demonstrated for TEX10-STAT3 in this study","pmids":["30045663"],"is_preprint":false},{"year":2023,"finding":"TEX10 physically interacts with STAT3 and promotes p300-mediated STAT3 acetylation, thereby enhancing STAT3 transcriptional activity and driving HCC cell invasion, EMT, and metastasis. Silencing p300 abolishes TEX10-enhanced STAT3 transcriptional activity.","method":"Co-immunoprecipitation, immunofluorescence, ChIP, dual-luciferase reporter assay, xenograft/lung metastasis models","journal":"Molecular carcinogenesis","confidence":"Medium","confidence_rationale":"Tier 2 — direct Co-IP interaction plus functional epistasis (p300 knockdown rescues) and ChIP validation, single lab","pmids":["37792308"],"is_preprint":false},{"year":2019,"finding":"TEX10 promotes stemness and epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma through activation of Wnt/β-catenin signaling; TEX10 knockdown inhibits proliferation, induces apoptosis/cell cycle arrest, and reduces stemness and invasiveness.","method":"Knockdown (lentiviral shRNA), Western blot, flow cytometry, Transwell invasion, sphere formation, CCK-8 assay","journal":"Oncology reports","confidence":"Low","confidence_rationale":"Tier 3 — functional KO with pathway readout, no direct biochemical mechanism for TEX10-Wnt interaction established","pmids":["31638260"],"is_preprint":false},{"year":2021,"finding":"TEX10 interacts with and stabilizes XRCC6 (Ku70) in bladder carcinoma cells, thereby activating Wnt/β-catenin signaling and DNA repair pathways, promoting tumor growth and radiotherapy resistance; TEX10 knockout reduces radiotherapy resistance.","method":"Co-immunoprecipitation, knockdown/knockout, xenograft, irradiation resistance assay","journal":"Journal of immunology research","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP interaction with functional phenotype, single lab, limited mechanistic detail","pmids":["34966825"],"is_preprint":false},{"year":2025,"finding":"TEX10 binds H3K4me3-marked promoters of Psmd3 and Psmd7 (negative regulators of Wnt signaling) and activates their expression, thereby restraining Wnt signaling during ESC-to-PGCLC differentiation and spermatogenesis. Tex10 conditional knockout mice show spermatocyte arrest at metaphase I and reduced sperm number/motility; Tex10 depletion and overexpression respectively compromise and enhance PGCLC differentiation efficiency.","method":"Conditional knockout mice, dTAG-degron ESCs, ChIP-seq (H3K4me3 occupancy), bulk and single-cell RNA-seq, ESC-to-PGCLC differentiation assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including chromatin occupancy, gain/loss-of-function genetics, scRNA-seq, and in vivo mouse models with defined molecular mechanism","pmids":["39988597"],"is_preprint":false},{"year":2023,"finding":"Tex10 binds to Wnt negative regulator gene loci marked by H3K4me3 at the PGCLC stage to restrain Wnt signaling; depletion hyperactivates and overexpression attenuates Wnt signaling, with corresponding effects on PGCLC specification efficiency. Tex10 conditional knockout mice display compromised round spermatid formation associated with aberrant Wnt signaling upregulation.","method":"ChIP-seq, conditional knockout mice, single-cell RNA-seq, PGCLC differentiation assay, sperm motility/count analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — ChIP-seq plus genetic loss/gain-of-function with scRNA-seq, preprint not yet peer-reviewed at time of corpus retrieval","pmids":["36865339"],"is_preprint":true},{"year":2022,"finding":"TEX10 and LINC00624 form a co-regulatory axis that stimulates NF-κB activity to promote proliferation and migration of prostate cancer cells; LINC00624 knockdown decreases TEX10-dependent NF-κB activation.","method":"In vitro knockdown, in vivo xenograft, NF-κB reporter/pathway analysis, co-expression analysis","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 — functional co-regulatory axis described but direct physical TEX10-LINC00624 interaction mechanism not biochemically resolved","pmids":["35219000"],"is_preprint":false}],"current_model":"TEX10 is a pluripotency-associated nuclear factor that binds super-enhancers and H3K4me3-marked promoters in a Sox2-dependent manner to coordinate histone acetylation (via p300) and DNA demethylation (via Tet1) for transcriptional activation; it physically interacts with Sox2, Pcgf3/5, p300, STAT3, and RELA to modulate context-dependent transcriptional programs, and fine-tunes Wnt signaling by activating expression of negative Wnt regulators (Psmd3/Psmd7), with essential roles in ESC self-renewal, primordial germ cell development, and spermatogenesis, while its dysregulation in cancer contexts activates NF-κB, STAT3, and Wnt/β-catenin signaling to promote tumor growth and therapy resistance."},"narrative":{"teleology":[{"year":2015,"claim":"The first mechanistic question—how TEX10 functions in stem cells—was answered by showing it is recruited to super-enhancers by Sox2 and coordinates p300-mediated histone acetylation and Tet1-mediated DNA demethylation to sustain pluripotency.","evidence":"Co-IP/MS, ChIP-seq, bisulfite sequencing, and knockdown/knockout phenotypic assays in mouse ESCs and reprogramming systems","pmids":["25936917"],"confidence":"High","gaps":["Structural basis for TEX10–Sox2 interaction undefined","Whether TEX10 has intrinsic enzymatic activity or functions purely as a scaffold unknown","Genome-wide target selectivity beyond super-enhancers not characterized"]},{"year":2017,"claim":"The upstream dependency of TEX10 chromatin recruitment was established: Pcgf3/5 (non-canonical PRC1 subunits) are required for TEX10 and p300 occupancy at target gene promoters, positioning TEX10 within a Pcgf3/5→TEX10→p300 activation axis for mesoderm differentiation genes.","evidence":"AP-MS interactomics, ChIP-seq occupancy changes upon CRISPR-Cas9 Pcgf3/5 double knockout, RNA-seq in mouse ESCs","pmids":["29054931"],"confidence":"High","gaps":["Direct versus bridged interaction between TEX10 and Pcgf3/5 not resolved","Whether TEX10 is a stable subunit of a defined Pcgf3/5-containing complex or transiently recruited unknown"]},{"year":2018,"claim":"TEX10 was implicated in cancer stemness for the first time, with knockdown reducing stem cell markers and chemoresistance in hepatocellular carcinoma, linked to decreased STAT3 pathway activity.","evidence":"shRNA/siRNA knockdown, sphere formation, drug resistance assays, and xenograft models in HCC cell lines","pmids":["30045663"],"confidence":"Low","gaps":["No direct TEX10–STAT3 physical interaction demonstrated in this study","Mechanism connecting TEX10 to STAT3 activation not biochemically defined","Single-lab finding without independent replication"]},{"year":2020,"claim":"A direct mechanism for TEX10 in NF-κB signaling was established: TEX10 physically interacts with RELA (p65) and enhances its nuclear localization and promoter occupancy, driving expression of pro-tumorigenic targets in colorectal cancer.","evidence":"Co-IP, ChIP, nuclear/cytoplasmic fractionation, shRNA library screen, in vivo xenograft in CRC models","pmids":["32995120"],"confidence":"Medium","gaps":["Domain mapping of TEX10–RELA interaction not performed","Whether TEX10's role in NF-κB activation is independent of its chromatin remodeling function unclear","Single-lab study"]},{"year":2023,"claim":"The earlier STAT3 link was mechanistically resolved: TEX10 physically interacts with STAT3 and promotes its p300-mediated acetylation, enhancing STAT3 transcriptional activity; p300 silencing abolishes TEX10-driven STAT3 activation, establishing an epistatic TEX10→p300→STAT3 axis in HCC metastasis.","evidence":"Co-IP, ChIP, dual-luciferase reporter, immunofluorescence, xenograft/lung metastasis models in HCC cells","pmids":["37792308"],"confidence":"Medium","gaps":["Whether TEX10 recruits p300 to STAT3 or stabilizes a pre-existing p300–STAT3 complex not distinguished","Relevance of this axis outside HCC not tested"]},{"year":2025,"claim":"TEX10's physiological role in germ cell development was defined: it binds H3K4me3-marked promoters of Psmd3 and Psmd7 to activate their expression, restraining Wnt signaling during PGCLC specification and spermatogenesis; conditional knockout mice exhibit metaphase I arrest and reduced sperm number/motility.","evidence":"Conditional knockout mice, dTAG-degron ESCs, ChIP-seq, bulk and single-cell RNA-seq, PGCLC differentiation assays","pmids":["39988597"],"confidence":"High","gaps":["How TEX10 recognizes H3K4me3-marked loci (direct histone binding or via a reader protein) not resolved","Whether TEX10's Wnt-restraining function operates in somatic tissues or is germ cell-specific unknown","Relationship between the super-enhancer role (Sox2-dependent) and H3K4me3-promoter role (Wnt regulation) not integrated"]},{"year":null,"claim":"A unified structural and biochemical understanding of TEX10's molecular activity—whether it possesses intrinsic enzymatic function or acts solely as a scaffold/adaptor—remains unresolved, as does the basis for its context-dependent switching between transcriptional activation in stem/germ cells and oncogenic signaling co-activation in cancer.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal/cryo-EM structure of TEX10 or its complexes available","No in vitro reconstitution demonstrating direct enzymatic activity","Mechanism by which TEX10 switches between super-enhancer, promoter, and NF-κB/STAT3 co-activation modes undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,2,4,7]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[7]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,2,7]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0,7]}],"pathway":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,7]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,1,7]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,4,7]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,7]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[7]}],"complexes":["Pcgf3/5–TEX10–p300 transcriptional activation complex"],"partners":["SOX2","PCGF3","PCGF5","EP300","TET1","RELA","STAT3","XRCC6"],"other_free_text":[]},"mechanistic_narrative":"TEX10 is a chromatin-associated transcriptional co-activator that coordinates histone acetylation and DNA demethylation to regulate pluripotency, germ cell development, and context-dependent gene expression programs. In embryonic stem cells, TEX10 localizes to super-enhancers in a Sox2-dependent manner and recruits p300 and Tet1 to sustain self-renewal, acting downstream of the non-canonical PRC1 components Pcgf3/5 [PMID:25936917, PMID:29054931]. TEX10 also binds H3K4me3-marked promoters of Wnt-pathway negative regulators (Psmd3/Psmd7) to restrain Wnt signaling during primordial germ cell-like cell specification and spermatogenesis, and conditional knockout in mice causes spermatocyte arrest at metaphase I [PMID:39988597]. In cancer contexts, TEX10 co-opts its transcriptional co-activator function to enhance NF-κB signaling by promoting RELA nuclear localization and to augment STAT3 transcriptional activity via p300-mediated STAT3 acetylation [PMID:32995120, PMID:37792308]."},"prefetch_data":{"uniprot":{"accession":"Q9NXF1","full_name":"Testis-expressed protein 10","aliases":[],"length_aa":929,"mass_kda":105.7,"function":"Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211)","subcellular_location":"Nucleus, nucleoplasm; Cytoplasm; Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9NXF1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TEX10","classification":"Common 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LAS1L","url":"https://www.omim.org/entry/300964"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TEX10"},"hgnc":{"alias_symbol":["FLJ20287","bA208F1.2","Ipi1"],"prev_symbol":[]},"alphafold":{"accession":"Q9NXF1","domains":[{"cath_id":"-","chopping":"399-404_428-536","consensus_level":"medium","plddt":87.1275,"start":399,"end":536},{"cath_id":"-","chopping":"682-846","consensus_level":"high","plddt":87.9846,"start":682,"end":846},{"cath_id":"-","chopping":"859-929","consensus_level":"medium","plddt":74.4885,"start":859,"end":929}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXF1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXF1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXF1-F1-predicted_aligned_error_v6.png","plddt_mean":80.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TEX10","jax_strain_url":"https://www.jax.org/strain/search?query=TEX10"},"sequence":{"accession":"Q9NXF1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NXF1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NXF1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXF1"}},"corpus_meta":[{"pmid":"25936917","id":"PMC_25936917","title":"Tex10 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\"pmids\": [\"25936917\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TEX10 interacts with Tet1 and p300 to regulate super-enhancers and sustain pluripotency in embryonic stem cells.\",\n      \"method\": \"Co-IP/protein interaction assays and functional ESC studies (as summarized in commentary)\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — referenced in commentary citing primary data from PMID:25936917; single lab\",\n      \"pmids\": [\"26046753\", \"25936917\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TEX10 interacts with Pcgf3/5 (polycomb group RING finger proteins) and p300, and Pcgf3/5 deletion substantially reduces TEX10 and p300 occupancy at target gene promoters, implicating TEX10 in a transcriptional activation complex in ESCs.\",\n      \"method\": \"Proteomic/interactome approaches, promoter occupancy (ChIP), Co-IP, CRISPR-Cas9 KO of Pcgf3/5 combined with RNA-seq\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction confirmed by proteomics and ChIP occupancy; multiple orthogonal methods\",\n      \"pmids\": [\"29054931\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TEX10 interacts with RELA (NF-κB p65 subunit), increases its nuclear localization, promotes RELA occupancy at gene promoters (including TNFAIP8, SAT1, IL6ST), and thereby promotes NF-κB-dependent proliferation in colorectal cancer cells.\",\n      \"method\": \"RNAi screen, Co-immunoprecipitation, nuclear/cytoplasmic fractionation, ChIP, gene expression analysis, in vitro and in vivo KD experiments\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, ChIP, fractionation, and in vivo validation provide multiple orthogonal lines of evidence\",\n      \"pmids\": [\"32995120\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TEX10 promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma through activation of the STAT3 signaling pathway.\",\n      \"method\": \"KD experiments (shRNA), stem cell marker expression assays, drug resistance assays, pathway analysis\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — functional KD with phenotypic readout and pathway identification, but mechanistic link to STAT3 is inferred rather than directly demonstrated by interaction studies in this paper\",\n      \"pmids\": [\"30045663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TEX10 promotes epithelial-mesenchymal transition (EMT) and stem cell-like features in esophageal squamous cell carcinoma via activation of Wnt/β-catenin signaling.\",\n      \"method\": \"shRNA knockdown, Western blot for EMT and Wnt pathway markers, sphere formation, Transwell migration/invasion, flow cytometry\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — KD with specific pathway readouts; mechanistic link to Wnt/β-catenin is based on marker changes rather than direct biochemical interaction\",\n      \"pmids\": [\"31638260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TEX10 stabilizes XRCC6 (Ku70) to promote DNA repair and Wnt/β-catenin signaling, thereby contributing to radiotherapy resistance in bladder carcinoma.\",\n      \"method\": \"Gene KO, in vitro proliferation/metastasis assays, xenograft, pathway analysis (Wnt/β-catenin and DNA repair channel), radiation resistance assay\",\n      \"journal\": \"Journal of immunology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — mechanistic link to XRCC6 stabilization is stated but limited biochemical detail is provided in the abstract\",\n      \"pmids\": [\"34966825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"LINC00624 and TEX10 form a co-regulatory axis that stimulates NF-κB activity to promote proliferation and migration of prostate cancer cells.\",\n      \"method\": \"In vitro knockdown assays, in vivo xenograft, mechanistic analysis of LINC00624-TEX10-NF-κB axis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — co-regulatory axis proposed; limited biochemical detail on direct interaction mechanism in abstract\",\n      \"pmids\": [\"35219000\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TEX10 directly interacts with STAT3 (by co-immunoprecipitation) and promotes STAT3 transcriptional activity; TEX10 also promotes p300-mediated STAT3 acetylation, and p300 silencing abolishes TEX10-enhanced STAT3 transcriptional activity.\",\n      \"method\": \"Co-immunoprecipitation, dual-luciferase reporter assay, immunofluorescence, ChIP, p300 silencing rescue experiments, in vitro and in vivo tumor models\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct interaction shown by Co-IP, transcriptional activity by luciferase and ChIP, epistasis via p300 KD; multiple orthogonal methods\",\n      \"pmids\": [\"37792308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TEX10 binds H3K4me3-marked promoters of Psmd3 and Psmd7 (negative regulators of Wnt signaling) at the PGCLC stage to activate their expression and thereby restrain Wnt signaling, which is required for proper PGC specification.\",\n      \"method\": \"Chromatin occupancy (ChIP), bulk and single-cell RNA-seq, dTAG-degron ESCs and Tex10 conditional KO mice, ESC-to-PGCLC differentiation assays with depletion/overexpression\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — ChIP and scRNA-seq with genetic models; preprint status reduces confidence slightly\",\n      \"pmids\": [\"36865339\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEX10 binds H3K4me3-marked promoters of Psmd3 and Psmd7 (Wnt signaling negative regulators), activating their expression to restrain Wnt signaling; Tex10-null spermatocytes arrest at metaphase I, and Tex10 depletion compromises ESC-to-PGCLC differentiation while overexpression enhances it.\",\n      \"method\": \"Chromatin occupancy assays, bulk and single-cell RNA sequencing, conditional knockout mice, dTAG-degron ESC system, ESC-to-PGCLC differentiation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct chromatin occupancy, genetic animal models, multiple orthogonal approaches, published in peer-reviewed journal\",\n      \"pmids\": [\"39988597\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEX10 is a pluripotency-associated nuclear factor that is recruited to super-enhancers and H3K4me3-marked promoters in a Sox2-dependent manner, where it forms complexes with p300, Tet1, and polycomb proteins (Pcgf3/5) to coordinate histone acetylation and DNA demethylation for transcriptional activation; in cancer contexts it drives oncogenic signaling by directly interacting with RELA (promoting nuclear NF-κB activity) and STAT3 (promoting p300-mediated STAT3 acetylation and transcriptional activity); and in germ cell/spermatogenesis contexts it binds promoters of Wnt pathway negative regulators (Psmd3/Psmd7) to restrain Wnt signaling required for primordial germ cell specification and proper spermatocyte progression through meiosis.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"TEX10 was identified as a Sox2-interacting protein that is enriched at super-enhancers (SEs) in embryonic stem cells in a Sox2-dependent manner. TEX10 coordinates histone acetylation and DNA demethylation at SEs, functioning together with Tet1 and p300 to sustain pluripotency. Loss of TEX10 impairs ESC self-renewal, early embryo development, and somatic cell reprogramming.\",\n      \"method\": \"Protein interaction network analysis (Co-IP/MS), ChIP-seq, bisulfite sequencing, knockdown/knockout phenotypic assays in ESCs and reprogramming assays\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Co-IP, ChIP-seq, DNA methylation analysis, functional KO phenotypes) in a single foundational study, replicated in human cells\",\n      \"pmids\": [\"25936917\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TEX10 interacts with Pcgf3/5 (non-canonical PRC1 components) and the transcriptional co-activator p300 in embryonic stem cells. Pcgf3/5 deletion reduces occupancy of TEX10 and p300 at target gene promoters, placing TEX10 downstream of Pcgf3/5 in a transcriptional activation complex required for mesoderm differentiation genes.\",\n      \"method\": \"Proteomic interactome (AP-MS), ChIP-seq occupancy analysis, CRISPR-Cas9 single/double knockout, RNA-seq\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal proteomic identification plus chromatin occupancy validation and genetic epistasis via CRISPR KO\",\n      \"pmids\": [\"29054931\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TEX10 promotes proliferation of colorectal cancer cells by interacting with RELA (NF-κB p65) and increasing its nuclear localization, enhancing RELA occupancy at target gene promoters and driving expression of TNFAIP8, SAT1, and IL6ST.\",\n      \"method\": \"shRNA library screen, Co-IP, ChIP, nuclear/cytoplasmic fractionation, in vitro and in vivo tumor growth assays\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP interaction plus ChIP occupancy and functional nuclear localization data, single lab\",\n      \"pmids\": [\"32995120\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TEX10 promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma through activation of the STAT3 signaling pathway, as shown by decreased stem cell marker expression and drug resistance upon TEX10 knockdown.\",\n      \"method\": \"Knockdown (shRNA/siRNA), Western blot, sphere formation assay, drug resistance assay, xenograft\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — functional KO with pathway activation readout but no direct biochemical interaction demonstrated for TEX10-STAT3 in this study\",\n      \"pmids\": [\"30045663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TEX10 physically interacts with STAT3 and promotes p300-mediated STAT3 acetylation, thereby enhancing STAT3 transcriptional activity and driving HCC cell invasion, EMT, and metastasis. Silencing p300 abolishes TEX10-enhanced STAT3 transcriptional activity.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, ChIP, dual-luciferase reporter assay, xenograft/lung metastasis models\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct Co-IP interaction plus functional epistasis (p300 knockdown rescues) and ChIP validation, single lab\",\n      \"pmids\": [\"37792308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TEX10 promotes stemness and epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma through activation of Wnt/β-catenin signaling; TEX10 knockdown inhibits proliferation, induces apoptosis/cell cycle arrest, and reduces stemness and invasiveness.\",\n      \"method\": \"Knockdown (lentiviral shRNA), Western blot, flow cytometry, Transwell invasion, sphere formation, CCK-8 assay\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — functional KO with pathway readout, no direct biochemical mechanism for TEX10-Wnt interaction established\",\n      \"pmids\": [\"31638260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TEX10 interacts with and stabilizes XRCC6 (Ku70) in bladder carcinoma cells, thereby activating Wnt/β-catenin signaling and DNA repair pathways, promoting tumor growth and radiotherapy resistance; TEX10 knockout reduces radiotherapy resistance.\",\n      \"method\": \"Co-immunoprecipitation, knockdown/knockout, xenograft, irradiation resistance assay\",\n      \"journal\": \"Journal of immunology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP interaction with functional phenotype, single lab, limited mechanistic detail\",\n      \"pmids\": [\"34966825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEX10 binds H3K4me3-marked promoters of Psmd3 and Psmd7 (negative regulators of Wnt signaling) and activates their expression, thereby restraining Wnt signaling during ESC-to-PGCLC differentiation and spermatogenesis. Tex10 conditional knockout mice show spermatocyte arrest at metaphase I and reduced sperm number/motility; Tex10 depletion and overexpression respectively compromise and enhance PGCLC differentiation efficiency.\",\n      \"method\": \"Conditional knockout mice, dTAG-degron ESCs, ChIP-seq (H3K4me3 occupancy), bulk and single-cell RNA-seq, ESC-to-PGCLC differentiation assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including chromatin occupancy, gain/loss-of-function genetics, scRNA-seq, and in vivo mouse models with defined molecular mechanism\",\n      \"pmids\": [\"39988597\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Tex10 binds to Wnt negative regulator gene loci marked by H3K4me3 at the PGCLC stage to restrain Wnt signaling; depletion hyperactivates and overexpression attenuates Wnt signaling, with corresponding effects on PGCLC specification efficiency. Tex10 conditional knockout mice display compromised round spermatid formation associated with aberrant Wnt signaling upregulation.\",\n      \"method\": \"ChIP-seq, conditional knockout mice, single-cell RNA-seq, PGCLC differentiation assay, sperm motility/count analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — ChIP-seq plus genetic loss/gain-of-function with scRNA-seq, preprint not yet peer-reviewed at time of corpus retrieval\",\n      \"pmids\": [\"36865339\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TEX10 and LINC00624 form a co-regulatory axis that stimulates NF-κB activity to promote proliferation and migration of prostate cancer cells; LINC00624 knockdown decreases TEX10-dependent NF-κB activation.\",\n      \"method\": \"In vitro knockdown, in vivo xenograft, NF-κB reporter/pathway analysis, co-expression analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — functional co-regulatory axis described but direct physical TEX10-LINC00624 interaction mechanism not biochemically resolved\",\n      \"pmids\": [\"35219000\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEX10 is a pluripotency-associated nuclear factor that binds super-enhancers and H3K4me3-marked promoters in a Sox2-dependent manner to coordinate histone acetylation (via p300) and DNA demethylation (via Tet1) for transcriptional activation; it physically interacts with Sox2, Pcgf3/5, p300, STAT3, and RELA to modulate context-dependent transcriptional programs, and fine-tunes Wnt signaling by activating expression of negative Wnt regulators (Psmd3/Psmd7), with essential roles in ESC self-renewal, primordial germ cell development, and spermatogenesis, while its dysregulation in cancer contexts activates NF-κB, STAT3, and Wnt/β-catenin signaling to promote tumor growth and therapy resistance.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TEX10 is a nuclear transcriptional co-activator that integrates epigenetic signaling at enhancers and promoters to regulate pluripotency, germ cell development, and oncogenic transcription programs. In embryonic stem cells, TEX10 is recruited to super-enhancers in a Sox2-dependent manner and cooperates with p300 and Tet1 to coordinate histone acetylation and DNA demethylation, while also forming a transcriptional activation complex with Pcgf3/5 at target gene promoters [PMID:25936917, PMID:29054931]. In germ cells, TEX10 binds H3K4me3-marked promoters of Wnt pathway negative regulators Psmd3 and Psmd7 to restrain Wnt signaling required for primordial germ cell specification, and Tex10-null spermatocytes arrest at metaphase I of meiosis [PMID:39988597]. In cancer cells, TEX10 directly interacts with RELA to promote nuclear NF-κB activity and with STAT3 to enhance p300-mediated STAT3 acetylation and transcriptional output, driving proliferation and stemness [PMID:32995120, PMID:37792308].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"The discovery that TEX10 is a Sox2-interacting protein enriched at super-enhancers in ESCs established it as an epigenetic co-activator linking transcription factor occupancy to histone acetylation and DNA demethylation at pluripotency loci.\",\n      \"evidence\": \"Co-IP, ChIP-seq, bisulfite sequencing, and loss-of-function studies in mouse ESCs and reprogramming assays\",\n      \"pmids\": [\"25936917\", \"26046753\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether TEX10 possesses intrinsic enzymatic activity or acts solely as a scaffold\",\n        \"Structural basis of TEX10 interaction with Sox2, Tet1, and p300\",\n        \"Whether TEX10 chromatin occupancy is fully Sox2-dependent or also mediated by other factors\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identification of Pcgf3/5 as TEX10 partners whose deletion reduces TEX10 and p300 occupancy at promoters revealed that non-canonical polycomb components recruit TEX10 into a transcriptional activation complex, resolving how TEX10 reaches specific genomic loci beyond super-enhancers.\",\n      \"evidence\": \"Proteomic interactome analysis, ChIP occupancy studies, CRISPR-Cas9 knockout of Pcgf3/5 with RNA-seq in ESCs\",\n      \"pmids\": [\"29054931\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether TEX10–Pcgf3/5 interaction is direct or bridged by additional subunits\",\n        \"Genome-wide overlap of TEX10 occupancy with Pcgf3/5 versus Sox2-defined sites\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstration that TEX10 physically interacts with RELA, promotes its nuclear retention and chromatin binding at NF-κB target genes, and drives proliferation in colorectal cancer cells extended TEX10's role from a stem cell factor to an oncogenic transcriptional co-activator operating through NF-κB signaling.\",\n      \"evidence\": \"Reciprocal Co-IP, nuclear/cytoplasmic fractionation, ChIP at NF-κB targets, RNAi screen, in vivo xenograft knockdown in colorectal cancer cells\",\n      \"pmids\": [\"32995120\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Domain on TEX10 responsible for RELA interaction\",\n        \"Whether TEX10–RELA interaction depends on inflammatory stimulation or is constitutive\",\n        \"Relationship between TEX10's p300 recruitment role and NF-κB acetylation\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Direct interaction between TEX10 and STAT3, together with epistatic evidence that p300 silencing abolishes TEX10-enhanced STAT3 transcriptional activity, established a p300-dependent mechanism through which TEX10 promotes STAT3 acetylation and target gene activation in cancer.\",\n      \"evidence\": \"Co-IP, dual-luciferase reporter assays, ChIP, p300 knockdown rescue, immunofluorescence, in vitro and in vivo tumor models\",\n      \"pmids\": [\"37792308\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether TEX10 bridges STAT3 and p300 simultaneously in a ternary complex\",\n        \"Whether the TEX10–STAT3 axis operates in normal physiology or only in cancer contexts\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"ChIP-based demonstration that TEX10 binds H3K4me3-marked promoters of Psmd3/Psmd7 to restrain Wnt signaling, combined with Tex10-null spermatocyte arrest at metaphase I, established TEX10 as a germ cell–essential factor that tempers Wnt activity during both PGC specification and meiotic progression.\",\n      \"evidence\": \"Chromatin occupancy assays, bulk and single-cell RNA-seq, conditional knockout mice, dTAG-degron ESC system, ESC-to-PGCLC differentiation assays\",\n      \"pmids\": [\"39988597\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How TEX10 is recruited specifically to H3K4me3-marked Psmd3/Psmd7 promoters — reader domain or adaptor mediated\",\n        \"Whether metaphase I arrest reflects spindle assembly checkpoint activation or direct meiotic machinery defects\",\n        \"Whether TEX10 restrains Wnt signaling in somatic tissues as well\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis for TEX10's scaffold function — how it simultaneously engages transcription factors (Sox2, RELA, STAT3), epigenetic writers (p300, Tet1), and chromatin readers (H3K4me3 recognition) — remains unresolved, and no enzymatic activity has been attributed to TEX10 itself.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure of TEX10 or any TEX10-containing complex\",\n        \"No domain-mapping studies defining interaction surfaces for its diverse partners\",\n        \"Whether TEX10 has any intrinsic catalytic activity\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 2, 3, 8, 10]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3, 8, 10]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 2, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2, 3, 8, 10]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 5, 8, 10]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 10]}\n    ],\n    \"complexes\": [\n      \"TEX10–p300–Tet1 super-enhancer complex\",\n      \"TEX10–Pcgf3/5–p300 activation complex\"\n    ],\n    \"partners\": [\n      \"SOX2\",\n      \"EP300\",\n      \"TET1\",\n      \"PCGF3\",\n      \"PCGF5\",\n      \"RELA\",\n      \"STAT3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"TEX10 is a chromatin-associated transcriptional co-activator that coordinates histone acetylation and DNA demethylation to regulate pluripotency, germ cell development, and context-dependent gene expression programs. In embryonic stem cells, TEX10 localizes to super-enhancers in a Sox2-dependent manner and recruits p300 and Tet1 to sustain self-renewal, acting downstream of the non-canonical PRC1 components Pcgf3/5 [PMID:25936917, PMID:29054931]. TEX10 also binds H3K4me3-marked promoters of Wnt-pathway negative regulators (Psmd3/Psmd7) to restrain Wnt signaling during primordial germ cell-like cell specification and spermatogenesis, and conditional knockout in mice causes spermatocyte arrest at metaphase I [PMID:39988597]. In cancer contexts, TEX10 co-opts its transcriptional co-activator function to enhance NF-κB signaling by promoting RELA nuclear localization and to augment STAT3 transcriptional activity via p300-mediated STAT3 acetylation [PMID:32995120, PMID:37792308].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"The first mechanistic question—how TEX10 functions in stem cells—was answered by showing it is recruited to super-enhancers by Sox2 and coordinates p300-mediated histone acetylation and Tet1-mediated DNA demethylation to sustain pluripotency.\",\n      \"evidence\": \"Co-IP/MS, ChIP-seq, bisulfite sequencing, and knockdown/knockout phenotypic assays in mouse ESCs and reprogramming systems\",\n      \"pmids\": [\"25936917\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis for TEX10–Sox2 interaction undefined\",\n        \"Whether TEX10 has intrinsic enzymatic activity or functions purely as a scaffold unknown\",\n        \"Genome-wide target selectivity beyond super-enhancers not characterized\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The upstream dependency of TEX10 chromatin recruitment was established: Pcgf3/5 (non-canonical PRC1 subunits) are required for TEX10 and p300 occupancy at target gene promoters, positioning TEX10 within a Pcgf3/5→TEX10→p300 activation axis for mesoderm differentiation genes.\",\n      \"evidence\": \"AP-MS interactomics, ChIP-seq occupancy changes upon CRISPR-Cas9 Pcgf3/5 double knockout, RNA-seq in mouse ESCs\",\n      \"pmids\": [\"29054931\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct versus bridged interaction between TEX10 and Pcgf3/5 not resolved\",\n        \"Whether TEX10 is a stable subunit of a defined Pcgf3/5-containing complex or transiently recruited unknown\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"TEX10 was implicated in cancer stemness for the first time, with knockdown reducing stem cell markers and chemoresistance in hepatocellular carcinoma, linked to decreased STAT3 pathway activity.\",\n      \"evidence\": \"shRNA/siRNA knockdown, sphere formation, drug resistance assays, and xenograft models in HCC cell lines\",\n      \"pmids\": [\"30045663\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct TEX10–STAT3 physical interaction demonstrated in this study\",\n        \"Mechanism connecting TEX10 to STAT3 activation not biochemically defined\",\n        \"Single-lab finding without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A direct mechanism for TEX10 in NF-κB signaling was established: TEX10 physically interacts with RELA (p65) and enhances its nuclear localization and promoter occupancy, driving expression of pro-tumorigenic targets in colorectal cancer.\",\n      \"evidence\": \"Co-IP, ChIP, nuclear/cytoplasmic fractionation, shRNA library screen, in vivo xenograft in CRC models\",\n      \"pmids\": [\"32995120\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Domain mapping of TEX10–RELA interaction not performed\",\n        \"Whether TEX10's role in NF-κB activation is independent of its chromatin remodeling function unclear\",\n        \"Single-lab study\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The earlier STAT3 link was mechanistically resolved: TEX10 physically interacts with STAT3 and promotes its p300-mediated acetylation, enhancing STAT3 transcriptional activity; p300 silencing abolishes TEX10-driven STAT3 activation, establishing an epistatic TEX10→p300→STAT3 axis in HCC metastasis.\",\n      \"evidence\": \"Co-IP, ChIP, dual-luciferase reporter, immunofluorescence, xenograft/lung metastasis models in HCC cells\",\n      \"pmids\": [\"37792308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether TEX10 recruits p300 to STAT3 or stabilizes a pre-existing p300–STAT3 complex not distinguished\",\n        \"Relevance of this axis outside HCC not tested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"TEX10's physiological role in germ cell development was defined: it binds H3K4me3-marked promoters of Psmd3 and Psmd7 to activate their expression, restraining Wnt signaling during PGCLC specification and spermatogenesis; conditional knockout mice exhibit metaphase I arrest and reduced sperm number/motility.\",\n      \"evidence\": \"Conditional knockout mice, dTAG-degron ESCs, ChIP-seq, bulk and single-cell RNA-seq, PGCLC differentiation assays\",\n      \"pmids\": [\"39988597\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How TEX10 recognizes H3K4me3-marked loci (direct histone binding or via a reader protein) not resolved\",\n        \"Whether TEX10's Wnt-restraining function operates in somatic tissues or is germ cell-specific unknown\",\n        \"Relationship between the super-enhancer role (Sox2-dependent) and H3K4me3-promoter role (Wnt regulation) not integrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unified structural and biochemical understanding of TEX10's molecular activity—whether it possesses intrinsic enzymatic function or acts solely as a scaffold/adaptor—remains unresolved, as does the basis for its context-dependent switching between transcriptional activation in stem/germ cells and oncogenic signaling co-activation in cancer.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal/cryo-EM structure of TEX10 or its complexes available\",\n        \"No in vitro reconstitution demonstrating direct enzymatic activity\",\n        \"Mechanism by which TEX10 switches between super-enhancer, promoter, and NF-κB/STAT3 co-activation modes undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 2, 4, 7]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 2, 7]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 7]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 4, 7]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 7]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [\n      \"Pcgf3/5–TEX10–p300 transcriptional activation complex\"\n    ],\n    \"partners\": [\n      \"SOX2\",\n      \"PCGF3\",\n      \"PCGF5\",\n      \"EP300\",\n      \"TET1\",\n      \"RELA\",\n      \"STAT3\",\n      \"XRCC6\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}