{"gene":"TAF6","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":1993,"finding":"Human TAFII70 (TAF6) binds weakly to TBP and tightly to TAFII250; together with TBP and TAFII250 forms a stable ternary complex; also directly interacts with dTAFII40 (TAF9 ortholog). Interactions are conserved between Drosophila TAFII60 and human TAFII70.","method":"Recombinant protein expression, coimmunoprecipitation, ternary complex formation assays","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding assays with recombinant proteins, multiple interaction partners tested, single lab","pmids":["8262073"],"is_preprint":false},{"year":1995,"finding":"Human TAFII80 (TAF6) interacts with TAFII250, TAFII31, TAFII20, and TBP, but not TAFII55; also interacts with TFIIE alpha and TFIIF alpha (RAP74) but not TFIIB, TFIIE beta, or TFIIF beta (RAP30). Mutational analysis defined three distinct interaction domains: N-terminus (residues 1–100) for TAFII31 and TAFII20, C-terminal region (residues 203–276) for TAFII250 and TFIIF alpha, and C-terminal region (residues 377–505) for TBP and TFIIE alpha.","method":"Coimmunoprecipitation with recombinant and expressed proteins; deletion/mutation mapping","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP with multiple partners, domain mapping by mutagenesis, multiple orthogonal interaction tests in a single rigorous study","pmids":["7667268"],"is_preprint":false},{"year":1997,"finding":"The histone fold motifs of human TAFII80 (TAF6) and TAFII22 are indispensable for their mutual interaction, supporting a histone octamer-like partial TAF complex within TFIID.","method":"Yeast two-hybrid system with deletion/mutation constructs targeting histone fold motifs","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid mutagenesis, single lab, single method","pmids":["9133630"],"is_preprint":false},{"year":1998,"finding":"N-CoR (and splice variants RIP13a and RIP13Delta1) directly interacts with TAFII70 (TAF6) in vitro. N-CoR can simultaneously interact with TFIIB, TAFII32, and TAFII70 in a non-competitive manner, and N-CoR expression ablates the functional interaction between TFIIB and TAFII32 required for transcription initiation.","method":"In vitro binding assays, co-immunoprecipitation in vivo, functional transcription assays","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo Co-IP, functional assay, single lab, multiple orthogonal methods","pmids":["9611234"],"is_preprint":false},{"year":2001,"finding":"TAFII70 (TAF6) protein localizes to Cajal bodies in the germinal vesicle (nucleus) of newt oocytes, associating with both chromosome-attached and free Cajal bodies, supporting a role for Cajal bodies as assembly sites for the transcription machinery.","method":"Immunostaining with anti-hTAFII70 monoclonal antibody; microinjection of myc-tagged PwTAFII70 transcripts into oocyte cytoplasm followed by detection in Cajal bodies","journal":"Genome","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by antibody staining and injection/expression, two orthogonal localization methods, single lab","pmids":["11768213"],"is_preprint":false},{"year":2004,"finding":"The TAFII70 isoform (but not TAFII80 isoform) of TAF6 causes G2 arrest and growth suppression of breast epithelial cells in a p53-independent manner, and uniquely forms a protein-protein interaction with GADD45a; GADD45a-null cells are resistant to TAFII70-mediated growth inhibition, establishing GADD45a as functionally required downstream.","method":"Isoform overexpression in cell lines, cell cycle analysis, co-immunoprecipitation of TAFII70-GADD45a interaction, GADD45a null cell epistasis experiment","journal":"Molecular cancer research : MCR","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, epistasis with null cells, isoform specificity demonstrated, single lab, multiple methods","pmids":["15328371"],"is_preprint":false},{"year":2012,"finding":"The C-terminal domain of TAF6 contains five conserved HEAT repeats (crystal structure at 1.9 Å from Antonospora locustae TAF6C). Mutations in the HEAT repeat domain impair TAF6-TAF9 interaction beyond just the histone fold motifs; TAF5 modulates the TAF6-TAF9 interaction, further weakening it in a TAF5-TAF6-TAF9 ternary context.","method":"X-ray crystallography (1.9 Å); site-directed mutagenesis in full-length human TAF6; co-immunoprecipitation in HeLa cells; ternary complex pulldown assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus mutagenesis plus Co-IP in human cells, multiple orthogonal methods in a single rigorous study","pmids":["22696218"],"is_preprint":false},{"year":2018,"finding":"In yeast, TAF6's histone-fold domain (HFD) is required for TAF6-TAF9 heterodimerization in vitro but is dispensable for TFIID/SAGA association in cell extracts; the HEAT repeat domain is required for TAF6's interaction with SAGA (but not TFIID) and for resistance to transcription elongation inhibitors; both HFD and HEAT domain mutations abolish TFIID and SAGA promoter occupancy. Genetic suppression: HEAT domain mutant temperature-sensitivity is suppressed by overexpression of TAF9, TAF12, or TBP; HFD mutant is suppressed by TAF5 but not TAF9, TAF12, or TBP.","method":"Yeast genetics (ts mutants), co-immunoprecipitation, ChIP assays, recombinant protein heterodimerization, genetic suppressor analysis","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (ChIP, Co-IP, in vitro reconstitution, genetic epistasis), systematic mutational dissection of two domains","pmids":["29485702"],"is_preprint":false},{"year":2025,"finding":"Non-catalytic FLOS domain of SETD1A is essential for TAF6 expression in gastric cancer cells; TAF6 acts downstream of SETD1A's non-catalytic function (established by CRISPR screen and cDNA rescue), and both SETD1A and TAF6 are required for G1/S cell cycle progression. E2F4 supports TAF6 expression upstream of SETD1A.","method":"Pooled CRISPR screen, cDNA rescue experiment, cell cycle analysis, expression knockdown","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR screen plus cDNA rescue establishes pathway position, single lab, functional cell cycle readout","pmids":["40846851"],"is_preprint":false},{"year":2025,"finding":"In human SAGA, the TAF6L HEAT repeat domain provides a docking surface for the splicing-factor module (SPL); structural differences between TAF6L (SAGA-specific) and canonical TAF6 (TFIID) are directly implicated in structural rearrangements required to accommodate SPL into SAGA.","method":"Cryo-EM structure of endogenous human SAGA purified by affinity-ligand without CRISPR engineering","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure but preprint, single study, applies to TAF6L paralog (SAGA-specific); relevant to TAF6 family mechanism","pmids":["bio_10.1101_2025.07.31.667873"],"is_preprint":true},{"year":2026,"finding":"TAF6 physically interacts with p53 (established by co-immunoprecipitation); lncRNA ZBTB46-AS1 competes with p53 for TAF6 binding, attenuating TAF6-p53 interaction and suppressing p53 transcriptional activity and p21 expression in ovarian cancer cells.","method":"RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation, dual-luciferase reporter assay","journal":"American journal of translational research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and functional reporter assays, multiple orthogonal methods, single lab","pmids":["41868912"],"is_preprint":false}],"current_model":"TAF6 (TAFII70/TAFII80) is a histone H4-like histone fold domain-containing subunit of both TFIID and SAGA complexes that heterodimerizes with TAF9 (via both its histone fold and HEAT repeat domains), interacts with multiple TFIID subunits (TAF250, TAF31, TAF20, TBP) and general transcription factors (TFIIE alpha, TFIIF alpha), serves as a platform for corepressor N-CoR to lock the transcription initiation machinery in an inactive state, has isoform-specific growth-suppressive activity linked to GADD45a interaction, supports G1/S cell cycle progression downstream of SETD1A via an E2F4-regulated axis, and can interact with p53 to support its transcriptional activity—with the HEAT repeat domain playing a structurally distinct role from the histone fold domain in SAGA versus TFIID assembly."},"narrative":{"mechanistic_narrative":"TAF6 (TAFII70/TAFII80) is a core architectural subunit of the general transcription machinery that organizes protein-protein contacts within TFIID and SAGA and bridges these complexes to regulatory factors [PMID:7667268, PMID:29485702]. Within TFIID it nucleates assembly through a histone-fold domain that drives heterodimerization with TAF9 (TAFII22) in a histone octamer-like arrangement, while a C-terminal domain comprising five conserved HEAT repeats provides a structurally distinct interaction surface that also contributes to TAF9 binding and is modulated by TAF5 [PMID:9133630, PMID:22696218]. The histone fold and HEAT domains have non-equivalent roles in complex assembly: in yeast the HFD supports TAF6-TAF9 heterodimerization while the HEAT domain is specifically required for SAGA association and resistance to elongation inhibitors, with both domains needed for TFIID and SAGA promoter occupancy; in human SAGA the TAF6L HEAT surface docks the splicing-factor module [PMID:29485702, PMID:bio_10.1101_2025.07.31.667873]. TAF6 establishes a defined network of contacts through three mapped interaction domains, binding TAF1 (TAFII250), TAF4 (TAFII31), TAF11 (TAFII20), and TBP among TFIID subunits and the general factors TFIIE alpha and TFIIF alpha (RAP74) [PMID:7667268, PMID:9133630]. It also serves as a platform for transcriptional control: the corepressor N-CoR binds TAF6 and locks the initiation machinery in an inactive state by ablating the TFIIB-TAF6/TAF11 interactions required for initiation [PMID:9611234]. TAF6 supports cell cycle progression and tumor-relevant transcription, acting downstream of the non-catalytic function of SETD1A in an E2F4-regulated axis to drive G1/S progression [PMID:40846851], exhibiting isoform-specific growth suppression through interaction with GADD45a [PMID:15328371], and physically interacting with p53 to support its transcriptional output [PMID:41868912].","teleology":[{"year":1993,"claim":"Established TAF6 as a stable TFIID subunit by showing it binds TBP and TAFII250 to form a ternary complex, defining its role in scaffolding the core TFIID architecture.","evidence":"Recombinant protein expression and coimmunoprecipitation/ternary complex assays, including conservation with Drosophila TAFII60","pmids":["8262073"],"confidence":"Medium","gaps":["Did not map the interaction surfaces","Functional consequence for transcription not tested"]},{"year":1995,"claim":"Resolved how TAF6 integrates into the transcription machinery by mapping three distinct interaction domains for TFIID subunits, TBP, and general transcription factors, defining it as a multi-contact hub.","evidence":"Reciprocal Co-IP with recombinant/expressed proteins plus deletion and mutation mapping","pmids":["7667268"],"confidence":"High","gaps":["Structural basis of the contacts not resolved","Functional requirement of each contact for transcription untested"]},{"year":1997,"claim":"Showed the histone fold motif drives TAF6 heterodimerization with TAF9/TAFII22, supporting a histone octamer-like sub-assembly inside TFIID.","evidence":"Yeast two-hybrid with histone-fold-targeted deletion/mutation constructs","pmids":["9133630"],"confidence":"Medium","gaps":["Single method (Y2H)","Did not address contributions of regions outside the histone fold"]},{"year":1998,"claim":"Linked TAF6 to active transcriptional repression by showing the corepressor N-CoR binds TAF6 and disrupts the TFIIB-TAF interactions needed for initiation.","evidence":"In vitro binding, in vivo Co-IP, and functional transcription assays","pmids":["9611234"],"confidence":"Medium","gaps":["N-CoR binding site on TAF6 not mapped","Promoter context and physiological targets unaddressed"]},{"year":2001,"claim":"Identified Cajal bodies as a subnuclear site where TAF6 accumulates, implicating these structures in assembly of the transcription machinery.","evidence":"Antibody immunostaining and microinjection/expression of tagged TAF6 in newt oocyte germinal vesicles","pmids":["11768213"],"confidence":"Medium","gaps":["Functional role of Cajal-body localization not established","Observed in oocytes; somatic relevance unclear"]},{"year":2004,"claim":"Revealed isoform-specific function by showing the TAFII70 isoform, but not TAFII80, induces G2 arrest and growth suppression through a required GADD45a interaction independent of p53.","evidence":"Isoform overexpression, cell cycle analysis, Co-IP, and epistasis in GADD45a-null cells","pmids":["15328371"],"confidence":"Medium","gaps":["Mechanism connecting TAF6 isoform to GADD45a-dependent arrest unknown","Endogenous isoform balance not quantified"]},{"year":2012,"claim":"Defined the C-terminal HEAT repeat domain at atomic resolution and demonstrated it contributes to TAF9 binding beyond the histone fold, with TAF5 modulating the interaction.","evidence":"1.9 A crystal structure (A. locustae TAF6C), site-directed mutagenesis of human TAF6, Co-IP, and ternary pulldowns","pmids":["22696218"],"confidence":"High","gaps":["Structure from an insect/microsporidian ortholog, not full-length human TFIID","Functional consequence of HEAT-mediated TAF9 binding in vivo untested here"]},{"year":2018,"claim":"Dissected the division of labor between TAF6 domains, showing the HFD drives TAF9 heterodimerization while the HEAT domain is selectively required for SAGA association and that both are needed for TFIID/SAGA promoter occupancy.","evidence":"Yeast ts mutants, Co-IP, ChIP, in vitro heterodimerization, and genetic suppressor analysis","pmids":["29485702"],"confidence":"High","gaps":["Performed in yeast; human SAGA-specific assignment not directly shown here","Molecular basis of HEAT-domain SAGA selectivity not resolved"]},{"year":2025,"claim":"Placed TAF6 in a SETD1A-dependent proliferation axis, showing TAF6 expression requires the non-catalytic FLOS domain of SETD1A and that TAF6 is needed for G1/S progression, with E2F4 acting upstream.","evidence":"Pooled CRISPR screen, cDNA rescue, knockdown, and cell cycle analysis in gastric cancer cells","pmids":["40846851"],"confidence":"Medium","gaps":["Direct transcriptional targets driving G1/S not identified","Mechanism by which SETD1A controls TAF6 expression unresolved"]},{"year":2025,"claim":"Showed structurally how the TAF6 HEAT surface specializes complex assembly, with the SAGA-specific paralog TAF6L HEAT domain providing the docking site for the splicing-factor module.","evidence":"Cryo-EM of endogenous human SAGA (preprint)","pmids":["bio_10.1101_2025.07.31.667873"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Applies to the TAF6L paralog rather than canonical TFIID TAF6"]},{"year":2026,"claim":"Connected TAF6 to p53-dependent transcription, showing a direct TAF6-p53 interaction that lncRNA ZBTB46-AS1 competitively disrupts to suppress p21 induction.","evidence":"RNA pull-down, RIP, Co-IP, and dual-luciferase reporter assays in ovarian cancer cells","pmids":["41868912"],"confidence":"Medium","gaps":["TAF6 region mediating p53 binding not mapped","Generality beyond ovarian cancer context untested"]},{"year":null,"claim":"How TAF6's two domains are differentially deployed to specify TFIID versus SAGA assembly in human cells, and how its contacts with regulators (N-CoR, p53, GADD45a) reshape initiation at specific promoters, remain mechanistically open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated structural model of human TFIID showing TAF6 regulatory contacts","Endogenous gene targets of TAF6-dependent regulation not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[3,8,10]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,2,6]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,3]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,3,7]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[5,8]}],"complexes":["TFIID","SAGA"],"partners":["TAF9","TAF1","TBP","TFIIE ALPHA","TFIIF ALPHA","NCOR1","GADD45A","TP53"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P49848","full_name":"Transcription initiation factor TFIID subunit 6","aliases":["RNA polymerase II TBP-associated factor subunit E","Transcription initiation factor TFIID 70 kDa subunit","TAF(II)70","TAFII-70","TAFII70","Transcription initiation factor TFIID 80 kDa subunit","TAF(II)80","TAFII-80","TAFII80"],"length_aa":677,"mass_kda":72.7,"function":"The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (PubMed:33795473). TAF6 homodimer connects TFIID modules, forming a rigid core (PubMed:33795473) Transcriptional regulator which acts primarily as a positive regulator of transcription (PubMed:20096117, PubMed:29358700). Recruited to the promoters of a number of genes including GADD45A and CDKN1A/p21, leading to transcriptional up-regulation and subsequent induction of apoptosis (PubMed:11583621). Also up-regulates expression of other genes including GCNA/ACRC, HES1 and IFFO1 (PubMed:18628956). In contrast, down-regulates transcription of MDM2 (PubMed:11583621). Acts as a transcriptional coactivator to enhance transcription of TP53/p53-responsive genes such as DUSP1 (PubMed:20096117). Can also activate transcription and apoptosis independently of TP53 (PubMed:18628956). Drives apoptosis via the intrinsic apoptotic pathway by up-regulating apoptosis effectors such as BCL2L11/BIM and PMAIP1/NOXA (PubMed:29358700)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P49848/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TAF6","classification":"Common Essential","n_dependent_lines":1206,"n_total_lines":1208,"dependency_fraction":0.9983443708609272},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TBP","stoichiometry":4.0},{"gene":"TAF12","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TAF6","total_profiled":1310},"omim":[{"mim_id":"617126","title":"ALAZAMI-YUAN SYNDROME; ALYUS","url":"https://www.omim.org/entry/617126"},{"mim_id":"609514","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 8; TAF8","url":"https://www.omim.org/entry/609514"},{"mim_id":"602955","title":"TAF6 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 80-KD; TAF6","url":"https://www.omim.org/entry/602955"},{"mim_id":"602946","title":"TAF6-LIKE RNA POLYMERASE II; TAF6L","url":"https://www.omim.org/entry/602946"},{"mim_id":"601796","title":"TAF4 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 135-KD; TAF4","url":"https://www.omim.org/entry/601796"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAF6"},"hgnc":{"alias_symbol":["TAFII70","TAFII80","MGC:8964","TAFII85"],"prev_symbol":["TAF2E"]},"alphafold":{"accession":"P49848","domains":[{"cath_id":"1.10.20.10","chopping":"14-89","consensus_level":"medium","plddt":86.6138,"start":14,"end":89},{"cath_id":"1.25.40.770","chopping":"219-384","consensus_level":"high","plddt":85.1843,"start":219,"end":384}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P49848","model_url":"https://alphafold.ebi.ac.uk/files/AF-P49848-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P49848-F1-predicted_aligned_error_v6.png","plddt_mean":63.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAF6","jax_strain_url":"https://www.jax.org/strain/search?query=TAF6"},"sequence":{"accession":"P49848","fasta_url":"https://rest.uniprot.org/uniprotkb/P49848.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P49848/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P49848"}},"corpus_meta":[{"pmid":"9611234","id":"PMC_9611234","title":"The corepressor N-CoR and its variants RIP13a and RIP13Delta1 directly interact with the basal transcription factors TFIIB, TAFII32 and TAFII70.","date":"1998","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/9611234","citation_count":114,"is_preprint":false},{"pmid":"7667268","id":"PMC_7667268","title":"Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors.","date":"1995","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/7667268","citation_count":75,"is_preprint":false},{"pmid":"8262073","id":"PMC_8262073","title":"Cloning and expression of Drosophila TAFII60 and human TAFII70 reveal conserved interactions with other subunits of TFIID.","date":"1993","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/8262073","citation_count":71,"is_preprint":false},{"pmid":"22696218","id":"PMC_22696218","title":"TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22696218","citation_count":24,"is_preprint":false},{"pmid":"9133630","id":"PMC_9133630","title":"The involvement of the histone fold motifs in the mutual interaction between human TAF(II)80 and TAF(II)22.","date":"1997","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9133630","citation_count":13,"is_preprint":false},{"pmid":"15328371","id":"PMC_15328371","title":"TAFII70 isoform-specific growth suppression correlates with its ability to complex with the GADD45a protein.","date":"2004","source":"Molecular cancer research : MCR","url":"https://pubmed.ncbi.nlm.nih.gov/15328371","citation_count":11,"is_preprint":false},{"pmid":"31899468","id":"PMC_31899468","title":"Proteomics and molecular network analyses reveal that the interaction between the TAT-DCF1 peptide and TAF6 induces an antitumor effect in glioma cells.","date":"2020","source":"Molecular omics","url":"https://pubmed.ncbi.nlm.nih.gov/31899468","citation_count":5,"is_preprint":false},{"pmid":"25025302","id":"PMC_25025302","title":"Alternative splicing of TAF6: downstream transcriptome impacts and upstream RNA splice control elements.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25025302","citation_count":5,"is_preprint":false},{"pmid":"11768213","id":"PMC_11768213","title":"TAFII70 protein in Cajal bodies of the amphibian germinal vesicle.","date":"2001","source":"Genome","url":"https://pubmed.ncbi.nlm.nih.gov/11768213","citation_count":4,"is_preprint":false},{"pmid":"29485702","id":"PMC_29485702","title":"Mutational analysis of TAF6 revealed the essential requirement of the histone-fold domain and the HEAT repeat domain for transcriptional activation.","date":"2018","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/29485702","citation_count":3,"is_preprint":false},{"pmid":"35317131","id":"PMC_35317131","title":"Novel compound heterozygous variants in the TAF6 gene in a patient with Alazami-Yuan syndrome: A case report.","date":"2022","source":"World journal of clinical cases","url":"https://pubmed.ncbi.nlm.nih.gov/35317131","citation_count":3,"is_preprint":false},{"pmid":"40846851","id":"PMC_40846851","title":"Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40846851","citation_count":2,"is_preprint":false},{"pmid":"39208271","id":"PMC_39208271","title":"Taenia solium TAF6 and TAF9 bind to a downstream promoter element present in the Tstbp1 gene core promoter.","date":"2024","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/39208271","citation_count":2,"is_preprint":false},{"pmid":"11091092","id":"PMC_11091092","title":"Expression of TAFII70 RNA and protein during oogenesis and development of the amphibian Pleurodeles waltl.","date":"2000","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/11091092","citation_count":1,"is_preprint":false},{"pmid":"41868912","id":"PMC_41868912","title":"Long non-coding RNA ZBTB46-AS1 promotes ovarian cancer progression through regulation of p53 activity by TAF6 protein.","date":"2026","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/41868912","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.31.667873","title":"Novel insights into the structure and evolution of the human SAGA complex by affinity-ligand purification","date":"2025-08-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.31.667873","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9578,"output_tokens":2991,"usd":0.036799,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10258,"output_tokens":3789,"usd":0.073008,"stage2_stop_reason":"end_turn"},"total_usd":0.109807,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"Human TAFII70 (TAF6) binds weakly to TBP and tightly to TAFII250; together with TBP and TAFII250 forms a stable ternary complex; also directly interacts with dTAFII40 (TAF9 ortholog). Interactions are conserved between Drosophila TAFII60 and human TAFII70.\",\n      \"method\": \"Recombinant protein expression, coimmunoprecipitation, ternary complex formation assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding assays with recombinant proteins, multiple interaction partners tested, single lab\",\n      \"pmids\": [\"8262073\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Human TAFII80 (TAF6) interacts with TAFII250, TAFII31, TAFII20, and TBP, but not TAFII55; also interacts with TFIIE alpha and TFIIF alpha (RAP74) but not TFIIB, TFIIE beta, or TFIIF beta (RAP30). Mutational analysis defined three distinct interaction domains: N-terminus (residues 1–100) for TAFII31 and TAFII20, C-terminal region (residues 203–276) for TAFII250 and TFIIF alpha, and C-terminal region (residues 377–505) for TBP and TFIIE alpha.\",\n      \"method\": \"Coimmunoprecipitation with recombinant and expressed proteins; deletion/mutation mapping\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP with multiple partners, domain mapping by mutagenesis, multiple orthogonal interaction tests in a single rigorous study\",\n      \"pmids\": [\"7667268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"The histone fold motifs of human TAFII80 (TAF6) and TAFII22 are indispensable for their mutual interaction, supporting a histone octamer-like partial TAF complex within TFIID.\",\n      \"method\": \"Yeast two-hybrid system with deletion/mutation constructs targeting histone fold motifs\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid mutagenesis, single lab, single method\",\n      \"pmids\": [\"9133630\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"N-CoR (and splice variants RIP13a and RIP13Delta1) directly interacts with TAFII70 (TAF6) in vitro. N-CoR can simultaneously interact with TFIIB, TAFII32, and TAFII70 in a non-competitive manner, and N-CoR expression ablates the functional interaction between TFIIB and TAFII32 required for transcription initiation.\",\n      \"method\": \"In vitro binding assays, co-immunoprecipitation in vivo, functional transcription assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo Co-IP, functional assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"9611234\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"TAFII70 (TAF6) protein localizes to Cajal bodies in the germinal vesicle (nucleus) of newt oocytes, associating with both chromosome-attached and free Cajal bodies, supporting a role for Cajal bodies as assembly sites for the transcription machinery.\",\n      \"method\": \"Immunostaining with anti-hTAFII70 monoclonal antibody; microinjection of myc-tagged PwTAFII70 transcripts into oocyte cytoplasm followed by detection in Cajal bodies\",\n      \"journal\": \"Genome\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by antibody staining and injection/expression, two orthogonal localization methods, single lab\",\n      \"pmids\": [\"11768213\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The TAFII70 isoform (but not TAFII80 isoform) of TAF6 causes G2 arrest and growth suppression of breast epithelial cells in a p53-independent manner, and uniquely forms a protein-protein interaction with GADD45a; GADD45a-null cells are resistant to TAFII70-mediated growth inhibition, establishing GADD45a as functionally required downstream.\",\n      \"method\": \"Isoform overexpression in cell lines, cell cycle analysis, co-immunoprecipitation of TAFII70-GADD45a interaction, GADD45a null cell epistasis experiment\",\n      \"journal\": \"Molecular cancer research : MCR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, epistasis with null cells, isoform specificity demonstrated, single lab, multiple methods\",\n      \"pmids\": [\"15328371\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The C-terminal domain of TAF6 contains five conserved HEAT repeats (crystal structure at 1.9 Å from Antonospora locustae TAF6C). Mutations in the HEAT repeat domain impair TAF6-TAF9 interaction beyond just the histone fold motifs; TAF5 modulates the TAF6-TAF9 interaction, further weakening it in a TAF5-TAF6-TAF9 ternary context.\",\n      \"method\": \"X-ray crystallography (1.9 Å); site-directed mutagenesis in full-length human TAF6; co-immunoprecipitation in HeLa cells; ternary complex pulldown assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus mutagenesis plus Co-IP in human cells, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"22696218\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In yeast, TAF6's histone-fold domain (HFD) is required for TAF6-TAF9 heterodimerization in vitro but is dispensable for TFIID/SAGA association in cell extracts; the HEAT repeat domain is required for TAF6's interaction with SAGA (but not TFIID) and for resistance to transcription elongation inhibitors; both HFD and HEAT domain mutations abolish TFIID and SAGA promoter occupancy. Genetic suppression: HEAT domain mutant temperature-sensitivity is suppressed by overexpression of TAF9, TAF12, or TBP; HFD mutant is suppressed by TAF5 but not TAF9, TAF12, or TBP.\",\n      \"method\": \"Yeast genetics (ts mutants), co-immunoprecipitation, ChIP assays, recombinant protein heterodimerization, genetic suppressor analysis\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (ChIP, Co-IP, in vitro reconstitution, genetic epistasis), systematic mutational dissection of two domains\",\n      \"pmids\": [\"29485702\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Non-catalytic FLOS domain of SETD1A is essential for TAF6 expression in gastric cancer cells; TAF6 acts downstream of SETD1A's non-catalytic function (established by CRISPR screen and cDNA rescue), and both SETD1A and TAF6 are required for G1/S cell cycle progression. E2F4 supports TAF6 expression upstream of SETD1A.\",\n      \"method\": \"Pooled CRISPR screen, cDNA rescue experiment, cell cycle analysis, expression knockdown\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR screen plus cDNA rescue establishes pathway position, single lab, functional cell cycle readout\",\n      \"pmids\": [\"40846851\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In human SAGA, the TAF6L HEAT repeat domain provides a docking surface for the splicing-factor module (SPL); structural differences between TAF6L (SAGA-specific) and canonical TAF6 (TFIID) are directly implicated in structural rearrangements required to accommodate SPL into SAGA.\",\n      \"method\": \"Cryo-EM structure of endogenous human SAGA purified by affinity-ligand without CRISPR engineering\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM structure but preprint, single study, applies to TAF6L paralog (SAGA-specific); relevant to TAF6 family mechanism\",\n      \"pmids\": [\"bio_10.1101_2025.07.31.667873\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TAF6 physically interacts with p53 (established by co-immunoprecipitation); lncRNA ZBTB46-AS1 competes with p53 for TAF6 binding, attenuating TAF6-p53 interaction and suppressing p53 transcriptional activity and p21 expression in ovarian cancer cells.\",\n      \"method\": \"RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation, dual-luciferase reporter assay\",\n      \"journal\": \"American journal of translational research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and functional reporter assays, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"41868912\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAF6 (TAFII70/TAFII80) is a histone H4-like histone fold domain-containing subunit of both TFIID and SAGA complexes that heterodimerizes with TAF9 (via both its histone fold and HEAT repeat domains), interacts with multiple TFIID subunits (TAF250, TAF31, TAF20, TBP) and general transcription factors (TFIIE alpha, TFIIF alpha), serves as a platform for corepressor N-CoR to lock the transcription initiation machinery in an inactive state, has isoform-specific growth-suppressive activity linked to GADD45a interaction, supports G1/S cell cycle progression downstream of SETD1A via an E2F4-regulated axis, and can interact with p53 to support its transcriptional activity—with the HEAT repeat domain playing a structurally distinct role from the histone fold domain in SAGA versus TFIID assembly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TAF6 (TAFII70/TAFII80) is a core architectural subunit of the general transcription machinery that organizes protein-protein contacts within TFIID and SAGA and bridges these complexes to regulatory factors [#1, #7]. Within TFIID it nucleates assembly through a histone-fold domain that drives heterodimerization with TAF9 (TAFII22) in a histone octamer-like arrangement, while a C-terminal domain comprising five conserved HEAT repeats provides a structurally distinct interaction surface that also contributes to TAF9 binding and is modulated by TAF5 [#2, #6]. The histone fold and HEAT domains have non-equivalent roles in complex assembly: in yeast the HFD supports TAF6-TAF9 heterodimerization while the HEAT domain is specifically required for SAGA association and resistance to elongation inhibitors, with both domains needed for TFIID and SAGA promoter occupancy; in human SAGA the TAF6L HEAT surface docks the splicing-factor module [#7, #9]. TAF6 establishes a defined network of contacts through three mapped interaction domains, binding TAF1 (TAFII250), TAF4 (TAFII31), TAF11 (TAFII20), and TBP among TFIID subunits and the general factors TFIIE alpha and TFIIF alpha (RAP74) [#1, #2]. It also serves as a platform for transcriptional control: the corepressor N-CoR binds TAF6 and locks the initiation machinery in an inactive state by ablating the TFIIB-TAF6/TAF11 interactions required for initiation [#3]. TAF6 supports cell cycle progression and tumor-relevant transcription, acting downstream of the non-catalytic function of SETD1A in an E2F4-regulated axis to drive G1/S progression [#8], exhibiting isoform-specific growth suppression through interaction with GADD45a [#5], and physically interacting with p53 to support its transcriptional output [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Established TAF6 as a stable TFIID subunit by showing it binds TBP and TAFII250 to form a ternary complex, defining its role in scaffolding the core TFIID architecture.\",\n      \"evidence\": \"Recombinant protein expression and coimmunoprecipitation/ternary complex assays, including conservation with Drosophila TAFII60\",\n      \"pmids\": [\"8262073\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not map the interaction surfaces\", \"Functional consequence for transcription not tested\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Resolved how TAF6 integrates into the transcription machinery by mapping three distinct interaction domains for TFIID subunits, TBP, and general transcription factors, defining it as a multi-contact hub.\",\n      \"evidence\": \"Reciprocal Co-IP with recombinant/expressed proteins plus deletion and mutation mapping\",\n      \"pmids\": [\"7667268\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Structural basis of the contacts not resolved\", \"Functional requirement of each contact for transcription untested\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Showed the histone fold motif drives TAF6 heterodimerization with TAF9/TAFII22, supporting a histone octamer-like sub-assembly inside TFIID.\",\n      \"evidence\": \"Yeast two-hybrid with histone-fold-targeted deletion/mutation constructs\",\n      \"pmids\": [\"9133630\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single method (Y2H)\", \"Did not address contributions of regions outside the histone fold\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Linked TAF6 to active transcriptional repression by showing the corepressor N-CoR binds TAF6 and disrupts the TFIIB-TAF interactions needed for initiation.\",\n      \"evidence\": \"In vitro binding, in vivo Co-IP, and functional transcription assays\",\n      \"pmids\": [\"9611234\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"N-CoR binding site on TAF6 not mapped\", \"Promoter context and physiological targets unaddressed\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identified Cajal bodies as a subnuclear site where TAF6 accumulates, implicating these structures in assembly of the transcription machinery.\",\n      \"evidence\": \"Antibody immunostaining and microinjection/expression of tagged TAF6 in newt oocyte germinal vesicles\",\n      \"pmids\": [\"11768213\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional role of Cajal-body localization not established\", \"Observed in oocytes; somatic relevance unclear\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Revealed isoform-specific function by showing the TAFII70 isoform, but not TAFII80, induces G2 arrest and growth suppression through a required GADD45a interaction independent of p53.\",\n      \"evidence\": \"Isoform overexpression, cell cycle analysis, Co-IP, and epistasis in GADD45a-null cells\",\n      \"pmids\": [\"15328371\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism connecting TAF6 isoform to GADD45a-dependent arrest unknown\", \"Endogenous isoform balance not quantified\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defined the C-terminal HEAT repeat domain at atomic resolution and demonstrated it contributes to TAF9 binding beyond the histone fold, with TAF5 modulating the interaction.\",\n      \"evidence\": \"1.9 A crystal structure (A. locustae TAF6C), site-directed mutagenesis of human TAF6, Co-IP, and ternary pulldowns\",\n      \"pmids\": [\"22696218\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Structure from an insect/microsporidian ortholog, not full-length human TFIID\", \"Functional consequence of HEAT-mediated TAF9 binding in vivo untested here\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Dissected the division of labor between TAF6 domains, showing the HFD drives TAF9 heterodimerization while the HEAT domain is selectively required for SAGA association and that both are needed for TFIID/SAGA promoter occupancy.\",\n      \"evidence\": \"Yeast ts mutants, Co-IP, ChIP, in vitro heterodimerization, and genetic suppressor analysis\",\n      \"pmids\": [\"29485702\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Performed in yeast; human SAGA-specific assignment not directly shown here\", \"Molecular basis of HEAT-domain SAGA selectivity not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed TAF6 in a SETD1A-dependent proliferation axis, showing TAF6 expression requires the non-catalytic FLOS domain of SETD1A and that TAF6 is needed for G1/S progression, with E2F4 acting upstream.\",\n      \"evidence\": \"Pooled CRISPR screen, cDNA rescue, knockdown, and cell cycle analysis in gastric cancer cells\",\n      \"pmids\": [\"40846851\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct transcriptional targets driving G1/S not identified\", \"Mechanism by which SETD1A controls TAF6 expression unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed structurally how the TAF6 HEAT surface specializes complex assembly, with the SAGA-specific paralog TAF6L HEAT domain providing the docking site for the splicing-factor module.\",\n      \"evidence\": \"Cryo-EM of endogenous human SAGA (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.07.31.667873\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Applies to the TAF6L paralog rather than canonical TFIID TAF6\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Connected TAF6 to p53-dependent transcription, showing a direct TAF6-p53 interaction that lncRNA ZBTB46-AS1 competitively disrupts to suppress p21 induction.\",\n      \"evidence\": \"RNA pull-down, RIP, Co-IP, and dual-luciferase reporter assays in ovarian cancer cells\",\n      \"pmids\": [\"41868912\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"TAF6 region mediating p53 binding not mapped\", \"Generality beyond ovarian cancer context untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TAF6's two domains are differentially deployed to specify TFIID versus SAGA assembly in human cells, and how its contacts with regulators (N-CoR, p53, GADD45a) reshape initiation at specific promoters, remain mechanistically open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No integrated structural model of human TFIID showing TAF6 regulatory contacts\", \"Endogenous gene targets of TAF6-dependent regulation not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [3, 8, 10]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 2, 6]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 3, 7]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [5, 8]}\n    ],\n    \"complexes\": [\"TFIID\", \"SAGA\"],\n    \"partners\": [\"TAF9\", \"TAF1\", \"TBP\", \"TFIIE alpha\", \"TFIIF alpha\", \"NCOR1\", \"GADD45A\", \"TP53\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}