{"gene":"TAF10","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":1994,"finding":"Human TAF10 (hTAFII30) is a component of a distinct subset of TFIID complexes and directly interacts with the AF-2-containing region E of the estrogen receptor (ER), mediating transcriptional activation by ER AF-2 but not VP16 or ER AF-1. An antibody against hTAFII30 selectively inhibited ER AF-2-mediated transcription without affecting basal or VP16-activated transcription, demonstrating functionally distinct TFIID populations.","method":"Co-immunoprecipitation, antibody inhibition of transcription in cell-free systems, separation of distinct TFIID complexes","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal biochemical methods, foundational study, highly cited","pmids":["7923369"],"is_preprint":false},{"year":1997,"finding":"TAF10 (TAFII30) stimulates transcription initiation ~20-fold in the presence of HMG-1 from an ERE-containing template in vitro, acting downstream of HMG-1-promoted ER-ERE binding, without itself affecting ER-ERE binding.","method":"In vitro transcription assay, EMSA with purified recombinant proteins","journal":"Molecular endocrinology","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution assay, single lab","pmids":["9212049"],"is_preprint":false},{"year":1999,"finding":"TAF10 (TAFII30) is required for cell cycle progression in murine F9 embryonal carcinoma cells; TAF10-null cells arrest in G1/G0, show impaired cyclin E expression, hypophosphorylated Rb, and undergo apoptosis. TAF10 is required for parietal endodermal differentiation but not primitive endodermal differentiation induced by retinoic acid.","method":"Homologous recombination gene targeting, Cre-loxP deletion, cell cycle analysis, Western blot, rescue with human TAF10","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — clean KO with specific cellular phenotype and molecular markers, well-controlled rescue","pmids":["10469660"],"is_preprint":false},{"year":2000,"finding":"Drosophila TAF10 homologs (dTAFII16 and dTAFII24) are components of dTFIID complexes, associating with TBP and other dTAFIIs; dTAFII24, but not dTAFII16, also associates with the histone acetyltransferase dGCN5, providing the first evidence for a TAF-GCN5-HAT complex in Drosophila.","method":"Co-immunoprecipitation, biochemical fractionation","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal co-IP for complex membership, single lab","pmids":["10669741"],"is_preprint":false},{"year":2003,"finding":"TAF10 is required for TFIID stability in vivo; TAF10-deficient mouse embryo cells express normal levels of TBP and other TAFs but contain only partially formed TFIID, are endocycle arrested, and have undetectable transcription levels. TAF10 loss is lethal in inner cell mass but not trophoblast cells.","method":"Cre-loxP conditional knockout in mice, biochemical analysis of TFIID integrity, transcriptional run-on assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — clean KO with molecular characterization of complex integrity and transcriptional output","pmids":["12773572"],"is_preprint":false},{"year":2004,"finding":"SET9 methyltransferase monomethylates TAF10 at a single lysine residue in the loop 2 region of its histone-fold domain. Methylated TAF10 has increased affinity for RNA polymerase II, pointing to a direct role in preinitiation complex formation. This modification potentiates transcription of a subset of TAF10-dependent genes in a promoter-specific manner correlated with SET9 recruitment.","method":"In vitro methylation assay, affinity binding assay (methylated vs. unmethylated TAF10 binding to RNA Pol II), reporter assays in TAF10-null F9 cells with methylation-deficient TAF10 mutant, ChIP","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro assay plus mutagenesis plus cellular rescue with defined mutant, multiple orthogonal methods","pmids":["15099517"],"is_preprint":false},{"year":2005,"finding":"TAF10 lacks an intrinsic nuclear localization signal (NLS) and depends on its histone-fold domain interaction partners (TAF8, TAF3, or SPT7L) for nuclear import. TAF8 and SPT7L carry NLS sequences that transport TAF10 to the nucleus; mutation of these NLS sequences retains TAF10 in the cytoplasm. TAF10 binds importin-beta in vitro only when co-expressed with TAF8 or TAF3 but not SPT7L. Once in the nucleus, FRAP shows TAF10 binds stably to nuclear structures.","method":"Fluorescent fusion protein localization, leptomycin B treatment, NLS mutagenesis, in vitro importin-beta binding assay, FRAP","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods including in vitro binding, mutagenesis, and live-cell imaging with functional consequence","pmids":["15870280"],"is_preprint":false},{"year":2005,"finding":"TAF10 ablation in keratinocytes of the developing foetal epidermis impairs keratinocyte terminal differentiation and skin permeability barrier function by affecting expression of a subset of genes, but loss of TAF10 in adult epidermis has no detectable effect on gene expression or epidermal homeostasis, demonstrating developmental stage-specific requirement.","method":"Conditional Cre-loxP deletion in keratinocytes, skin barrier assay, gene expression analysis","journal":"Developmental biology","confidence":"High","confidence_rationale":"Tier 2 — conditional KO with specific phenotypic readout showing context-dependent requirement","pmids":["16039642"],"is_preprint":false},{"year":2007,"finding":"TAF10 (TAFII30) mediates estrogen/ER-dependent repression of gene promoters by facilitating direct association of ER with core promoter sequences in a co-repressor complex containing SMRT and/or NCoR; this requires the E/F and DNA-binding domains of ER. Tamoxifen disrupts the ER-co-repressor complex at the promoter. TAFII30 is required for optimal core promoter activity and for the repressive association of ER.","method":"Biotinylated DNA pulldown from nuclear extracts, ChIP, siRNA knockdown, promoter-reporter assays, protein synthesis inhibition experiments","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2-3 — ChIP and pulldown with functional readout, single lab, moderate mechanistic depth","pmids":["17599049"],"is_preprint":false},{"year":2015,"finding":"TAF10 assembles with TAF2 and TAF8 into a heterotrimeric cytoplasmic subcomplex that is a precursor to nuclear holo-TFIID. TAF8 nucleates the complex; the TAF8-TAF10 histone fold domains adopt a non-canonical arrangement revealed by X-ray crystallography; TAF2 binds to multiple C-terminal motifs of TAF8, and these interactions dictate TAF2 incorporation into a nuclear core-TFIID complex.","method":"Native mass spectrometry, X-ray crystallography, co-immunoprecipitation, biochemical reconstitution, cellular fractionation","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 — crystal structure plus native MS plus biochemical reconstitution, multiple orthogonal methods","pmids":["25586196"],"is_preprint":false},{"year":2015,"finding":"LOXL2 enzymatically oxidizes methylated TAF10 (converting ε-amino groups of lysine to aldehyde groups), identified by unbiased proteomics. LOXL2-mediated oxidation of TAF10 induces its release from target promoters, blocking TFIID-dependent gene transcription and inactivating pluripotency genes in embryonic stem cells. Absence of LOXL2 in zebrafish results in aberrant Sox2 overexpression and impaired neural differentiation.","method":"Unbiased proteomic identification of LOXL2 substrates, ChIP showing TAF10 promoter release, ES cell pluripotency assays, zebrafish loss-of-function","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1-2 — proteomic identification plus ChIP plus in vivo zebrafish validation, multiple orthogonal methods","pmids":["25959397"],"is_preprint":false},{"year":2015,"finding":"TAF10 directly interacts with the GATA1 transcription factor as shown by co-immunoprecipitation and mass spectrometry; TAF10 is enriched on the GATA1 locus in human fetal erythroid cells by ChIP. Erythroid-specific ablation of TAF10 causes a differentiation block with deregulated GATA1 target genes including Gata1 itself.","method":"Co-immunoprecipitation, mass spectrometry, ChIP, conditional Cre-loxP deletion in erythroid cells","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — direct protein interaction confirmed by Co-IP/MS plus ChIP plus in vivo KO with specific phenotype","pmids":["25870109"],"is_preprint":false},{"year":2017,"finding":"TAF10 is required for assembly of both TFIID and SAGA complexes in the mouse embryo; conditional Taf10 deletion in presomitic mesoderm (PSM) shows that TAF10-containing canonical TFIID and SAGA are dispensable for cyclic gene transcription and PSM segmental patterning but required for lateral plate differentiation, demonstrating context-dependent transcriptional roles.","method":"Conditional Cre-loxP deletion, RNA-seq, complex integrity analysis","journal":"Development","confidence":"High","confidence_rationale":"Tier 2 — conditional KO with genome-wide transcriptional analysis and specific developmental phenotypes","pmids":["28893950"],"is_preprint":false},{"year":2017,"finding":"Drosophila TAF10 and TAF10b (dTAFII16 and dTAFII24) share interaction partners and have partially redundant functions; dTAF10b loss causes pupal lethality while dTAF10 loss allows puparium formation but causes eye morphology defects. During DNA repair, dTAF10 and dTAF10b act redundantly.","method":"Double-mutant generation, transgenic rescue, in silico structural modeling, DNA repair assays","journal":"Transcription","confidence":"Medium","confidence_rationale":"Tier 2-3 — genetic epistasis with rescue, single lab, Drosophila ortholog","pmids":["28841365"],"is_preprint":false},{"year":2023,"finding":"The E3 ligase TRIP12 induces TAF10 degradation via ubiquitination, which in turn reduces MYC protein levels; the small molecule Z363 activates TRIP12 to co-regulate both TAF10 and MYC, suppressing tumor growth.","method":"CRISPR/Cas9 KO, Western blot of TAF10/MYC levels, cell culture functional assays, mouse xenograft model","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 3 — functional cellular assays with mechanistic claim about E3 ligase-mediated TAF10 degradation, single lab","pmids":["36639831"],"is_preprint":false},{"year":2024,"finding":"METTL14 promotes m6A methylation of TAF10 mRNA, suppressing TAF10 mRNA stability and reducing TAF10 protein levels; this was demonstrated by methylated RNA immunoprecipitation, RNA immunoprecipitation, and luciferase reporter assay for TAF10 mRNA stability.","method":"RNA immunoprecipitation, methylated RNA immunoprecipitation (MeRIP), luciferase reporter assay for mRNA stability, Western blot, xenograft mouse model","journal":"Heliyon","confidence":"Medium","confidence_rationale":"Tier 2-3 — multiple RNA-level assays demonstrating m6A-mediated stability control, single lab","pmids":["38882361"],"is_preprint":false}],"current_model":"TAF10 is a histone-fold domain-containing subunit of both TFIID and SAGA/TFTC complexes that lacks an intrinsic NLS and is transported to the nucleus via interaction partners TAF8, TAF3, or SPT7L; it assembles into a cytoplasmic TAF2-TAF8-TAF10 heterotrimer as a precursor to nuclear holo-TFIID, directly contacts activators including the estrogen receptor and GATA1 to mediate gene-specific transcriptional activation, is monomethylated by SET9 at a histone-fold loop lysine to increase affinity for RNA Pol II and potentiate transcription of a subset of target genes, and is oxidized by LOXL2 on that methylated lysine to drive its release from promoters and repress TFIID-dependent transcription, while its overall protein stability is regulated by TRIP12-mediated ubiquitination and its mRNA stability is regulated by METTL14-mediated m6A methylation."},"narrative":{"teleology":[{"year":1994,"claim":"Establishing that TAF10 functions as a gene-specific bridge within TFIID resolved how a general transcription factor could selectively mediate activation by specific regulators such as estrogen receptor AF-2.","evidence":"Co-immunoprecipitation of distinct TFIID populations and antibody-inhibition of in vitro transcription in human cell-free systems","pmids":["7923369"],"confidence":"High","gaps":["No structural basis for the TAF10–ER interaction","Whether TAF10 contacts other activators was untested"]},{"year":1999,"claim":"Demonstrating that TAF10 loss causes G1 arrest, Rb hypophosphorylation, and apoptosis established that TAF10 is essential for cell viability and cell cycle progression, not merely modulatory.","evidence":"Cre-loxP knockout in murine F9 embryonal carcinoma cells with cell cycle analysis and rescue by human TAF10","pmids":["10469660"],"confidence":"High","gaps":["Whether the phenotype reflects TFIID destabilization or loss of a TAF10-specific function was unclear","Genome-wide transcriptional impact not measured"]},{"year":2003,"claim":"Showing that TAF10 deletion collapses TFIID integrity and abolishes transcription in mouse embryo cells resolved whether TAF10 is a peripheral modulator or an essential structural subunit of holo-TFIID.","evidence":"Conditional knockout in mouse embryo cells with biochemical fractionation of TFIID and transcriptional run-on assays","pmids":["12773572"],"confidence":"High","gaps":["Mechanism by which TAF10 stabilizes the full TFIID complex was unknown","Relative contribution of SAGA loss versus TFIID loss to phenotype was unresolved"]},{"year":2004,"claim":"Discovery that SET9 monomethylates TAF10 at a histone-fold lysine and that this increases RNA Pol II affinity revealed the first post-translational modification directly tuning a TAF's function within the preinitiation complex.","evidence":"In vitro methylation assay, affinity binding of methylated TAF10 to Pol II, reporter rescue in TAF10-null F9 cells with methylation-deficient mutant, ChIP for SET9","pmids":["15099517"],"confidence":"High","gaps":["Identity of the specific lysine residue number was not universally mapped across species","Whether other methyltransferases contribute was untested"]},{"year":2005,"claim":"Revealing that TAF10 lacks an intrinsic NLS and piggybacks on histone-fold partners for nuclear import answered how an essential transcription factor reaches the nucleus and implied cytoplasmic pre-assembly as a regulatory step.","evidence":"Fluorescent fusion localization, NLS mutagenesis, importin-β binding assays, FRAP in living cells","pmids":["15870280"],"confidence":"High","gaps":["How the choice among TAF8, TAF3, and SPT7L import routes is regulated was unknown","Whether cytoplasmic retention serves a regulatory function was untested"]},{"year":2005,"claim":"Context-dependent requirement of TAF10 was established by showing it is essential for fetal but not adult keratinocyte gene expression, revealing that TFIID/SAGA dependence varies with developmental state.","evidence":"Conditional Cre-loxP deletion in mouse keratinocytes, skin barrier assay, gene expression analysis","pmids":["16039642"],"confidence":"High","gaps":["Which alternative transcriptional machinery compensates in adult epidermis was unknown","Whether TAF10-independent transcription uses TBP-free or partial TFIID complexes was unresolved"]},{"year":2015,"claim":"Crystal structure of the TAF8–TAF10 histone-fold pair and reconstitution of the cytoplasmic TAF2–TAF8–TAF10 heterotrimer defined the molecular pathway of TFIID subcomplex assembly before nuclear import.","evidence":"X-ray crystallography, native mass spectrometry, co-immunoprecipitation, biochemical reconstitution","pmids":["25586196"],"confidence":"High","gaps":["How the heterotrimer is handed off to core-TFIID in the nucleus was not visualized","Kinetics of cytoplasmic assembly in vivo were unmeasured"]},{"year":2015,"claim":"Identification of LOXL2-mediated oxidation of methylated TAF10 as a mechanism to evict TAF10 from promoters established a two-step epigenetic switch—methylation then oxidation—controlling TFIID occupancy at pluripotency genes.","evidence":"Unbiased proteomic substrate identification, ChIP showing TAF10 promoter release, ES cell assays, zebrafish LOXL2 loss-of-function","pmids":["25959397"],"confidence":"High","gaps":["Whether oxidized TAF10 is degraded or recycled was unknown","Genome-wide map of LOXL2-sensitive versus LOXL2-insensitive TAF10 targets was not generated"]},{"year":2015,"claim":"Direct interaction between TAF10 and GATA1 and the block in erythroid differentiation upon TAF10 ablation extended the activator-bridging paradigm beyond ER to a hematopoietic lineage-determining factor.","evidence":"Co-immunoprecipitation, mass spectrometry, ChIP, conditional erythroid-specific Cre-loxP deletion","pmids":["25870109"],"confidence":"High","gaps":["Structural basis of TAF10–GATA1 interaction was undefined","Whether TAF10 contacts other hematopoietic transcription factors was untested"]},{"year":2017,"claim":"Demonstrating that TAF10-containing TFIID and SAGA are dispensable for cyclic gene transcription in presomitic mesoderm but required for lateral plate differentiation sharpened the model of tissue- and program-specific TFIID dependence.","evidence":"Conditional deletion in presomitic mesoderm, RNA-seq, complex integrity analysis in mouse embryos","pmids":["28893950"],"confidence":"High","gaps":["Identity of the TAF10-independent transcriptional machinery supporting cyclic genes was not determined","Whether partial TFIID or TBP-free complexes substitute remains unresolved"]},{"year":2023,"claim":"Identifying TRIP12 as the E3 ubiquitin ligase that degrades TAF10 revealed a proteolytic axis linking TFIID subunit turnover to MYC protein levels and tumor growth control.","evidence":"CRISPR/Cas9 knockout, Western blot, cell culture assays, mouse xenograft model","pmids":["36639831"],"confidence":"Medium","gaps":["Ubiquitination sites on TAF10 were not mapped","Whether TAF10 degradation is the sole mediator of MYC reduction was not fully dissected","Not independently confirmed by a second lab"]},{"year":2024,"claim":"Showing that METTL14-mediated m6A methylation of TAF10 mRNA reduces its stability added an epitranscriptomic layer of TAF10 regulation upstream of its protein-level modifications.","evidence":"MeRIP, RNA immunoprecipitation, luciferase mRNA stability reporter, Western blot, xenograft model","pmids":["38882361"],"confidence":"Medium","gaps":["Specific m6A sites on TAF10 mRNA were not mapped at nucleotide resolution","Reader protein(s) mediating the stability effect were not identified","Single-lab finding not independently replicated"]},{"year":null,"claim":"A unified structural model integrating SET9 methylation, LOXL2 oxidation, TRIP12 ubiquitination, and m6A-mediated mRNA control of TAF10 into a coherent regulatory circuit governing TFIID occupancy at specific promoters remains to be established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No integrative study has addressed how the multiple TAF10 modifications are temporally coordinated","Genome-wide identification of TAF10-dependent versus TAF10-independent promoters in a single system is lacking","Structural basis for activator selectivity (ER vs GATA1 vs others) through TAF10 is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[4,9,12]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,5,11]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[6,9]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,4,5,10,11,12]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2,7,11,12]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2]}],"complexes":["TFIID","SAGA/TFTC","TAF2-TAF8-TAF10 heterotrimer"],"partners":["TAF8","TAF2","TAF3","SPT7L","SET9","LOXL2","GATA1","TRIP12"],"other_free_text":[]},"mechanistic_narrative":"TAF10 is a histone-fold domain subunit shared by the TFIID and SAGA transcriptional co-activator complexes, serving as an essential scaffold for complex integrity and a direct contact point between the general transcription machinery and gene-specific activators. TAF10 assembles with TAF8 and TAF2 into a cytoplasmic heterotrimer that is a precursor to nuclear holo-TFIID; because TAF10 lacks an intrinsic NLS, it depends on histone-fold partners TAF8, TAF3, or SPT7L for nuclear import [PMID:15870280, PMID:25586196]. Loss of TAF10 destabilizes TFIID, arrests cell cycle progression, and blocks differentiation in a context-dependent manner—being essential in embryonic inner cell mass and fetal keratinocytes but dispensable in adult epidermis and presomitic mesoderm cyclic transcription [PMID:12773572, PMID:16039642, PMID:28893950]. TAF10 activity is tuned by SET9-mediated monomethylation of a histone-fold lysine, which increases RNA Pol II affinity and potentiates transcription at specific promoters, and by LOXL2-catalyzed oxidation of that methylated lysine, which triggers TAF10 release from promoters to repress TFIID-dependent transcription of pluripotency genes [PMID:15099517, PMID:25959397]."},"prefetch_data":{"uniprot":{"accession":"Q12962","full_name":"Transcription initiation factor TFIID subunit 10","aliases":["STAF28","Transcription initiation factor TFIID 30 kDa subunit","TAF(II)30","TAFII-30","TAFII30"],"length_aa":218,"mass_kda":21.7,"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). TAF10 is also component of the PCAF histone acetylase complex, the TATA-binding protein-free TAF complex (TFTC) and the STAGA transcription coactivator-HAT complex (PubMed:10373431, PubMed:11564863, PubMed:12601814, PubMed:18206972, PubMed:9885574). May regulate cyclin E expression (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q12962/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TAF10","classification":"Common Essential","n_dependent_lines":997,"n_total_lines":1208,"dependency_fraction":0.8253311258278145},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TAF12","stoichiometry":10.0},{"gene":"TBP","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TAF10","total_profiled":1310},"omim":[{"mim_id":"612762","title":"SPTY7-LIKE, STAGA COMPLEX SUBUNIT GAMMA; SUPT7L","url":"https://www.omim.org/entry/612762"},{"mim_id":"612116","title":"UBIQUITIN-SPECIFIC PROTEASE 22; USP22","url":"https://www.omim.org/entry/612116"},{"mim_id":"609514","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 8; TAF8","url":"https://www.omim.org/entry/609514"},{"mim_id":"606576","title":"TAF3 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 140-KD; TAF3","url":"https://www.omim.org/entry/606576"},{"mim_id":"602955","title":"TAF6 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 80-KD; TAF6","url":"https://www.omim.org/entry/602955"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAF10"},"hgnc":{"alias_symbol":["TAFII30"],"prev_symbol":["TAF2H","TAF2A"]},"alphafold":{"accession":"Q12962","domains":[{"cath_id":"1.10.20","chopping":"115-180_192-206","consensus_level":"medium","plddt":91.6921,"start":115,"end":206}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q12962","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q12962-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q12962-F1-predicted_aligned_error_v6.png","plddt_mean":66.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAF10","jax_strain_url":"https://www.jax.org/strain/search?query=TAF10"},"sequence":{"accession":"Q12962","fasta_url":"https://rest.uniprot.org/uniprotkb/Q12962.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q12962/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q12962"}},"corpus_meta":[{"pmid":"7923369","id":"PMC_7923369","title":"Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor.","date":"1994","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/7923369","citation_count":356,"is_preprint":false},{"pmid":"15099517","id":"PMC_15099517","title":"Gene-specific modulation of TAF10 function by SET9-mediated methylation.","date":"2004","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/15099517","citation_count":223,"is_preprint":false},{"pmid":"10469660","id":"PMC_10469660","title":"Mammalian TAF(II)30 is required for cell cycle progression and specific cellular differentiation programmes.","date":"1999","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/10469660","citation_count":82,"is_preprint":false},{"pmid":"25586196","id":"PMC_25586196","title":"Cytoplasmic TAF2-TAF8-TAF10 complex provides evidence for nuclear holo-TFIID assembly from preformed submodules.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25586196","citation_count":80,"is_preprint":false},{"pmid":"9212049","id":"PMC_9212049","title":"High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation.","date":"1997","source":"Molecular endocrinology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/9212049","citation_count":66,"is_preprint":false},{"pmid":"12773572","id":"PMC_12773572","title":"TAF10 (TAF(II)30) is necessary for TFIID stability and early embryogenesis in mice.","date":"2003","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12773572","citation_count":56,"is_preprint":false},{"pmid":"10669741","id":"PMC_10669741","title":"Two novel Drosophila TAF(II)s have homology with human TAF(II)30 and are differentially regulated during development.","date":"2000","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10669741","citation_count":52,"is_preprint":false},{"pmid":"15870280","id":"PMC_15870280","title":"The nuclear import of TAF10 is regulated by one of its three histone fold domain-containing interaction partners.","date":"2005","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15870280","citation_count":45,"is_preprint":false},{"pmid":"16039642","id":"PMC_16039642","title":"TAF10 is required for the establishment of skin barrier function in foetal, but not in adult mouse epidermis.","date":"2005","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/16039642","citation_count":45,"is_preprint":false},{"pmid":"25959397","id":"PMC_25959397","title":"LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation.","date":"2015","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/25959397","citation_count":42,"is_preprint":false},{"pmid":"25870109","id":"PMC_25870109","title":"TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis.","date":"2015","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/25870109","citation_count":20,"is_preprint":false},{"pmid":"17599049","id":"PMC_17599049","title":"Estrogen-induced and TAFII30-mediated gene repression by direct recruitment of the estrogen receptor and co-repressors to the core promoter and its reversal by tamoxifen.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17599049","citation_count":19,"is_preprint":false},{"pmid":"28893950","id":"PMC_28893950","title":"The TAF10-containing TFIID and SAGA transcriptional complexes are dispensable for early somitogenesis in the mouse embryo.","date":"2017","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/28893950","citation_count":16,"is_preprint":false},{"pmid":"17148695","id":"PMC_17148695","title":"Temporary expression of the TAF10 gene and its requirement for normal development of Arabidopsis thaliana.","date":"2006","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/17148695","citation_count":15,"is_preprint":false},{"pmid":"15659449","id":"PMC_15659449","title":"Abundant expression in vascular tissue of plant TAF10, an orthologous gene for TATA box-binding protein-associated factor 10, in Flaveria trinervia and abnormal morphology of Arabidopsis thaliana transformants on its overexpression.","date":"2005","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/15659449","citation_count":13,"is_preprint":false},{"pmid":"8530084","id":"PMC_8530084","title":"Organization and chromosomal localization of the gene (TAF2H) encoding the human TBP-associated factor II 30 (TAFII30).","date":"1995","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8530084","citation_count":11,"is_preprint":false},{"pmid":"38882361","id":"PMC_38882361","title":"METTL14 inhibits the malignant processes of gastric cancer cells by promoting N6-methyladenosine (m6A) methylation of TAF10.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38882361","citation_count":9,"is_preprint":false},{"pmid":"36639831","id":"PMC_36639831","title":"Small molecule Z363 co-regulates TAF10 and MYC via the E3 ligase TRIP12 to suppress tumour growth.","date":"2023","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36639831","citation_count":8,"is_preprint":false},{"pmid":"33069188","id":"PMC_33069188","title":"Deletions of the Idh1, Eco1, Rom2, and Taf10 Genes Differently Control the Hyphal Growth, Drug Tolerance, and Virulence of Candida albicans.","date":"2020","source":"Folia biologica","url":"https://pubmed.ncbi.nlm.nih.gov/33069188","citation_count":3,"is_preprint":false},{"pmid":"28841365","id":"PMC_28841365","title":"TAF10 and TAF10b partially redundant roles during Drosophila melanogaster morphogenesis.","date":"2017","source":"Transcription","url":"https://pubmed.ncbi.nlm.nih.gov/28841365","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10591,"output_tokens":3990,"usd":0.045811},"stage2":{"model":"claude-opus-4-6","input_tokens":7407,"output_tokens":3243,"usd":0.177165},"total_usd":0.222976,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"Human TAF10 (hTAFII30) is a component of a distinct subset of TFIID complexes and directly interacts with the AF-2-containing region E of the estrogen receptor (ER), mediating transcriptional activation by ER AF-2 but not VP16 or ER AF-1. An antibody against hTAFII30 selectively inhibited ER AF-2-mediated transcription without affecting basal or VP16-activated transcription, demonstrating functionally distinct TFIID populations.\",\n      \"method\": \"Co-immunoprecipitation, antibody inhibition of transcription in cell-free systems, separation of distinct TFIID complexes\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal biochemical methods, foundational study, highly cited\",\n      \"pmids\": [\"7923369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"TAF10 (TAFII30) stimulates transcription initiation ~20-fold in the presence of HMG-1 from an ERE-containing template in vitro, acting downstream of HMG-1-promoted ER-ERE binding, without itself affecting ER-ERE binding.\",\n      \"method\": \"In vitro transcription assay, EMSA with purified recombinant proteins\",\n      \"journal\": \"Molecular endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution assay, single lab\",\n      \"pmids\": [\"9212049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"TAF10 (TAFII30) is required for cell cycle progression in murine F9 embryonal carcinoma cells; TAF10-null cells arrest in G1/G0, show impaired cyclin E expression, hypophosphorylated Rb, and undergo apoptosis. TAF10 is required for parietal endodermal differentiation but not primitive endodermal differentiation induced by retinoic acid.\",\n      \"method\": \"Homologous recombination gene targeting, Cre-loxP deletion, cell cycle analysis, Western blot, rescue with human TAF10\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with specific cellular phenotype and molecular markers, well-controlled rescue\",\n      \"pmids\": [\"10469660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Drosophila TAF10 homologs (dTAFII16 and dTAFII24) are components of dTFIID complexes, associating with TBP and other dTAFIIs; dTAFII24, but not dTAFII16, also associates with the histone acetyltransferase dGCN5, providing the first evidence for a TAF-GCN5-HAT complex in Drosophila.\",\n      \"method\": \"Co-immunoprecipitation, biochemical fractionation\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP for complex membership, single lab\",\n      \"pmids\": [\"10669741\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TAF10 is required for TFIID stability in vivo; TAF10-deficient mouse embryo cells express normal levels of TBP and other TAFs but contain only partially formed TFIID, are endocycle arrested, and have undetectable transcription levels. TAF10 loss is lethal in inner cell mass but not trophoblast cells.\",\n      \"method\": \"Cre-loxP conditional knockout in mice, biochemical analysis of TFIID integrity, transcriptional run-on assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with molecular characterization of complex integrity and transcriptional output\",\n      \"pmids\": [\"12773572\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"SET9 methyltransferase monomethylates TAF10 at a single lysine residue in the loop 2 region of its histone-fold domain. Methylated TAF10 has increased affinity for RNA polymerase II, pointing to a direct role in preinitiation complex formation. This modification potentiates transcription of a subset of TAF10-dependent genes in a promoter-specific manner correlated with SET9 recruitment.\",\n      \"method\": \"In vitro methylation assay, affinity binding assay (methylated vs. unmethylated TAF10 binding to RNA Pol II), reporter assays in TAF10-null F9 cells with methylation-deficient TAF10 mutant, ChIP\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro assay plus mutagenesis plus cellular rescue with defined mutant, multiple orthogonal methods\",\n      \"pmids\": [\"15099517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"TAF10 lacks an intrinsic nuclear localization signal (NLS) and depends on its histone-fold domain interaction partners (TAF8, TAF3, or SPT7L) for nuclear import. TAF8 and SPT7L carry NLS sequences that transport TAF10 to the nucleus; mutation of these NLS sequences retains TAF10 in the cytoplasm. TAF10 binds importin-beta in vitro only when co-expressed with TAF8 or TAF3 but not SPT7L. Once in the nucleus, FRAP shows TAF10 binds stably to nuclear structures.\",\n      \"method\": \"Fluorescent fusion protein localization, leptomycin B treatment, NLS mutagenesis, in vitro importin-beta binding assay, FRAP\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods including in vitro binding, mutagenesis, and live-cell imaging with functional consequence\",\n      \"pmids\": [\"15870280\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"TAF10 ablation in keratinocytes of the developing foetal epidermis impairs keratinocyte terminal differentiation and skin permeability barrier function by affecting expression of a subset of genes, but loss of TAF10 in adult epidermis has no detectable effect on gene expression or epidermal homeostasis, demonstrating developmental stage-specific requirement.\",\n      \"method\": \"Conditional Cre-loxP deletion in keratinocytes, skin barrier assay, gene expression analysis\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO with specific phenotypic readout showing context-dependent requirement\",\n      \"pmids\": [\"16039642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"TAF10 (TAFII30) mediates estrogen/ER-dependent repression of gene promoters by facilitating direct association of ER with core promoter sequences in a co-repressor complex containing SMRT and/or NCoR; this requires the E/F and DNA-binding domains of ER. Tamoxifen disrupts the ER-co-repressor complex at the promoter. TAFII30 is required for optimal core promoter activity and for the repressive association of ER.\",\n      \"method\": \"Biotinylated DNA pulldown from nuclear extracts, ChIP, siRNA knockdown, promoter-reporter assays, protein synthesis inhibition experiments\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — ChIP and pulldown with functional readout, single lab, moderate mechanistic depth\",\n      \"pmids\": [\"17599049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TAF10 assembles with TAF2 and TAF8 into a heterotrimeric cytoplasmic subcomplex that is a precursor to nuclear holo-TFIID. TAF8 nucleates the complex; the TAF8-TAF10 histone fold domains adopt a non-canonical arrangement revealed by X-ray crystallography; TAF2 binds to multiple C-terminal motifs of TAF8, and these interactions dictate TAF2 incorporation into a nuclear core-TFIID complex.\",\n      \"method\": \"Native mass spectrometry, X-ray crystallography, co-immunoprecipitation, biochemical reconstitution, cellular fractionation\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure plus native MS plus biochemical reconstitution, multiple orthogonal methods\",\n      \"pmids\": [\"25586196\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"LOXL2 enzymatically oxidizes methylated TAF10 (converting ε-amino groups of lysine to aldehyde groups), identified by unbiased proteomics. LOXL2-mediated oxidation of TAF10 induces its release from target promoters, blocking TFIID-dependent gene transcription and inactivating pluripotency genes in embryonic stem cells. Absence of LOXL2 in zebrafish results in aberrant Sox2 overexpression and impaired neural differentiation.\",\n      \"method\": \"Unbiased proteomic identification of LOXL2 substrates, ChIP showing TAF10 promoter release, ES cell pluripotency assays, zebrafish loss-of-function\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — proteomic identification plus ChIP plus in vivo zebrafish validation, multiple orthogonal methods\",\n      \"pmids\": [\"25959397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TAF10 directly interacts with the GATA1 transcription factor as shown by co-immunoprecipitation and mass spectrometry; TAF10 is enriched on the GATA1 locus in human fetal erythroid cells by ChIP. Erythroid-specific ablation of TAF10 causes a differentiation block with deregulated GATA1 target genes including Gata1 itself.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, ChIP, conditional Cre-loxP deletion in erythroid cells\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct protein interaction confirmed by Co-IP/MS plus ChIP plus in vivo KO with specific phenotype\",\n      \"pmids\": [\"25870109\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TAF10 is required for assembly of both TFIID and SAGA complexes in the mouse embryo; conditional Taf10 deletion in presomitic mesoderm (PSM) shows that TAF10-containing canonical TFIID and SAGA are dispensable for cyclic gene transcription and PSM segmental patterning but required for lateral plate differentiation, demonstrating context-dependent transcriptional roles.\",\n      \"method\": \"Conditional Cre-loxP deletion, RNA-seq, complex integrity analysis\",\n      \"journal\": \"Development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO with genome-wide transcriptional analysis and specific developmental phenotypes\",\n      \"pmids\": [\"28893950\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Drosophila TAF10 and TAF10b (dTAFII16 and dTAFII24) share interaction partners and have partially redundant functions; dTAF10b loss causes pupal lethality while dTAF10 loss allows puparium formation but causes eye morphology defects. During DNA repair, dTAF10 and dTAF10b act redundantly.\",\n      \"method\": \"Double-mutant generation, transgenic rescue, in silico structural modeling, DNA repair assays\",\n      \"journal\": \"Transcription\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — genetic epistasis with rescue, single lab, Drosophila ortholog\",\n      \"pmids\": [\"28841365\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The E3 ligase TRIP12 induces TAF10 degradation via ubiquitination, which in turn reduces MYC protein levels; the small molecule Z363 activates TRIP12 to co-regulate both TAF10 and MYC, suppressing tumor growth.\",\n      \"method\": \"CRISPR/Cas9 KO, Western blot of TAF10/MYC levels, cell culture functional assays, mouse xenograft model\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — functional cellular assays with mechanistic claim about E3 ligase-mediated TAF10 degradation, single lab\",\n      \"pmids\": [\"36639831\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"METTL14 promotes m6A methylation of TAF10 mRNA, suppressing TAF10 mRNA stability and reducing TAF10 protein levels; this was demonstrated by methylated RNA immunoprecipitation, RNA immunoprecipitation, and luciferase reporter assay for TAF10 mRNA stability.\",\n      \"method\": \"RNA immunoprecipitation, methylated RNA immunoprecipitation (MeRIP), luciferase reporter assay for mRNA stability, Western blot, xenograft mouse model\",\n      \"journal\": \"Heliyon\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — multiple RNA-level assays demonstrating m6A-mediated stability control, single lab\",\n      \"pmids\": [\"38882361\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAF10 is a histone-fold domain-containing subunit of both TFIID and SAGA/TFTC complexes that lacks an intrinsic NLS and is transported to the nucleus via interaction partners TAF8, TAF3, or SPT7L; it assembles into a cytoplasmic TAF2-TAF8-TAF10 heterotrimer as a precursor to nuclear holo-TFIID, directly contacts activators including the estrogen receptor and GATA1 to mediate gene-specific transcriptional activation, is monomethylated by SET9 at a histone-fold loop lysine to increase affinity for RNA Pol II and potentiate transcription of a subset of target genes, and is oxidized by LOXL2 on that methylated lysine to drive its release from promoters and repress TFIID-dependent transcription, while its overall protein stability is regulated by TRIP12-mediated ubiquitination and its mRNA stability is regulated by METTL14-mediated m6A methylation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TAF10 is a histone-fold domain subunit shared by the TFIID and SAGA transcriptional co-activator complexes, serving as an essential scaffold for complex integrity and a direct contact point between the general transcription machinery and gene-specific activators. TAF10 assembles with TAF8 and TAF2 into a cytoplasmic heterotrimer that is a precursor to nuclear holo-TFIID; because TAF10 lacks an intrinsic NLS, it depends on histone-fold partners TAF8, TAF3, or SPT7L for nuclear import [PMID:15870280, PMID:25586196]. Loss of TAF10 destabilizes TFIID, arrests cell cycle progression, and blocks differentiation in a context-dependent manner—being essential in embryonic inner cell mass and fetal keratinocytes but dispensable in adult epidermis and presomitic mesoderm cyclic transcription [PMID:12773572, PMID:16039642, PMID:28893950]. TAF10 activity is tuned by SET9-mediated monomethylation of a histone-fold lysine, which increases RNA Pol II affinity and potentiates transcription at specific promoters, and by LOXL2-catalyzed oxidation of that methylated lysine, which triggers TAF10 release from promoters to repress TFIID-dependent transcription of pluripotency genes [PMID:15099517, PMID:25959397].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing that TAF10 functions as a gene-specific bridge within TFIID resolved how a general transcription factor could selectively mediate activation by specific regulators such as estrogen receptor AF-2.\",\n      \"evidence\": \"Co-immunoprecipitation of distinct TFIID populations and antibody-inhibition of in vitro transcription in human cell-free systems\",\n      \"pmids\": [\"7923369\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural basis for the TAF10–ER interaction\",\n        \"Whether TAF10 contacts other activators was untested\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Demonstrating that TAF10 loss causes G1 arrest, Rb hypophosphorylation, and apoptosis established that TAF10 is essential for cell viability and cell cycle progression, not merely modulatory.\",\n      \"evidence\": \"Cre-loxP knockout in murine F9 embryonal carcinoma cells with cell cycle analysis and rescue by human TAF10\",\n      \"pmids\": [\"10469660\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the phenotype reflects TFIID destabilization or loss of a TAF10-specific function was unclear\",\n        \"Genome-wide transcriptional impact not measured\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Showing that TAF10 deletion collapses TFIID integrity and abolishes transcription in mouse embryo cells resolved whether TAF10 is a peripheral modulator or an essential structural subunit of holo-TFIID.\",\n      \"evidence\": \"Conditional knockout in mouse embryo cells with biochemical fractionation of TFIID and transcriptional run-on assays\",\n      \"pmids\": [\"12773572\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which TAF10 stabilizes the full TFIID complex was unknown\",\n        \"Relative contribution of SAGA loss versus TFIID loss to phenotype was unresolved\"\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Discovery that SET9 monomethylates TAF10 at a histone-fold lysine and that this increases RNA Pol II affinity revealed the first post-translational modification directly tuning a TAF's function within the preinitiation complex.\",\n      \"evidence\": \"In vitro methylation assay, affinity binding of methylated TAF10 to Pol II, reporter rescue in TAF10-null F9 cells with methylation-deficient mutant, ChIP for SET9\",\n      \"pmids\": [\"15099517\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the specific lysine residue number was not universally mapped across species\",\n        \"Whether other methyltransferases contribute was untested\"\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Revealing that TAF10 lacks an intrinsic NLS and piggybacks on histone-fold partners for nuclear import answered how an essential transcription factor reaches the nucleus and implied cytoplasmic pre-assembly as a regulatory step.\",\n      \"evidence\": \"Fluorescent fusion localization, NLS mutagenesis, importin-β binding assays, FRAP in living cells\",\n      \"pmids\": [\"15870280\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How the choice among TAF8, TAF3, and SPT7L import routes is regulated was unknown\",\n        \"Whether cytoplasmic retention serves a regulatory function was untested\"\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Context-dependent requirement of TAF10 was established by showing it is essential for fetal but not adult keratinocyte gene expression, revealing that TFIID/SAGA dependence varies with developmental state.\",\n      \"evidence\": \"Conditional Cre-loxP deletion in mouse keratinocytes, skin barrier assay, gene expression analysis\",\n      \"pmids\": [\"16039642\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Which alternative transcriptional machinery compensates in adult epidermis was unknown\",\n        \"Whether TAF10-independent transcription uses TBP-free or partial TFIID complexes was unresolved\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Crystal structure of the TAF8–TAF10 histone-fold pair and reconstitution of the cytoplasmic TAF2–TAF8–TAF10 heterotrimer defined the molecular pathway of TFIID subcomplex assembly before nuclear import.\",\n      \"evidence\": \"X-ray crystallography, native mass spectrometry, co-immunoprecipitation, biochemical reconstitution\",\n      \"pmids\": [\"25586196\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How the heterotrimer is handed off to core-TFIID in the nucleus was not visualized\",\n        \"Kinetics of cytoplasmic assembly in vivo were unmeasured\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identification of LOXL2-mediated oxidation of methylated TAF10 as a mechanism to evict TAF10 from promoters established a two-step epigenetic switch—methylation then oxidation—controlling TFIID occupancy at pluripotency genes.\",\n      \"evidence\": \"Unbiased proteomic substrate identification, ChIP showing TAF10 promoter release, ES cell assays, zebrafish LOXL2 loss-of-function\",\n      \"pmids\": [\"25959397\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether oxidized TAF10 is degraded or recycled was unknown\",\n        \"Genome-wide map of LOXL2-sensitive versus LOXL2-insensitive TAF10 targets was not generated\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Direct interaction between TAF10 and GATA1 and the block in erythroid differentiation upon TAF10 ablation extended the activator-bridging paradigm beyond ER to a hematopoietic lineage-determining factor.\",\n      \"evidence\": \"Co-immunoprecipitation, mass spectrometry, ChIP, conditional erythroid-specific Cre-loxP deletion\",\n      \"pmids\": [\"25870109\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of TAF10–GATA1 interaction was undefined\",\n        \"Whether TAF10 contacts other hematopoietic transcription factors was untested\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrating that TAF10-containing TFIID and SAGA are dispensable for cyclic gene transcription in presomitic mesoderm but required for lateral plate differentiation sharpened the model of tissue- and program-specific TFIID dependence.\",\n      \"evidence\": \"Conditional deletion in presomitic mesoderm, RNA-seq, complex integrity analysis in mouse embryos\",\n      \"pmids\": [\"28893950\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the TAF10-independent transcriptional machinery supporting cyclic genes was not determined\",\n        \"Whether partial TFIID or TBP-free complexes substitute remains unresolved\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying TRIP12 as the E3 ubiquitin ligase that degrades TAF10 revealed a proteolytic axis linking TFIID subunit turnover to MYC protein levels and tumor growth control.\",\n      \"evidence\": \"CRISPR/Cas9 knockout, Western blot, cell culture assays, mouse xenograft model\",\n      \"pmids\": [\"36639831\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Ubiquitination sites on TAF10 were not mapped\",\n        \"Whether TAF10 degradation is the sole mediator of MYC reduction was not fully dissected\",\n        \"Not independently confirmed by a second lab\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showing that METTL14-mediated m6A methylation of TAF10 mRNA reduces its stability added an epitranscriptomic layer of TAF10 regulation upstream of its protein-level modifications.\",\n      \"evidence\": \"MeRIP, RNA immunoprecipitation, luciferase mRNA stability reporter, Western blot, xenograft model\",\n      \"pmids\": [\"38882361\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific m6A sites on TAF10 mRNA were not mapped at nucleotide resolution\",\n        \"Reader protein(s) mediating the stability effect were not identified\",\n        \"Single-lab finding not independently replicated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unified structural model integrating SET9 methylation, LOXL2 oxidation, TRIP12 ubiquitination, and m6A-mediated mRNA control of TAF10 into a coherent regulatory circuit governing TFIID occupancy at specific promoters remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No integrative study has addressed how the multiple TAF10 modifications are temporally coordinated\",\n        \"Genome-wide identification of TAF10-dependent versus TAF10-independent promoters in a single system is lacking\",\n        \"Structural basis for activator selectivity (ER vs GATA1 vs others) through TAF10 is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0005198\",\n        \"supporting_discovery_ids\": [4, 9, 12]\n      },\n      {\n        \"term_id\": \"GO:0140110\",\n        \"supporting_discovery_ids\": [0, 5, 11]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005634\",\n        \"supporting_discovery_ids\": [6, 9]\n      },\n      {\n        \"term_id\": \"GO:0005829\",\n        \"supporting_discovery_ids\": [6, 9]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-74160\",\n        \"supporting_discovery_ids\": [0, 4, 5, 10, 11, 12]\n      },\n      {\n        \"term_id\": \"R-HSA-1266738\",\n        \"supporting_discovery_ids\": [2, 7, 11, 12]\n      },\n      {\n        \"term_id\": \"R-HSA-1640170\",\n        \"supporting_discovery_ids\": [2]\n      }\n    ],\n    \"complexes\": [\n      \"TFIID\",\n      \"SAGA/TFTC\",\n      \"TAF2-TAF8-TAF10 heterotrimer\"\n    ],\n    \"partners\": [\n      \"TAF8\",\n      \"TAF2\",\n      \"TAF3\",\n      \"SPT7L\",\n      \"SET9\",\n      \"LOXL2\",\n      \"GATA1\",\n      \"TRIP12\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}