{"gene":"TAF7","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2001,"finding":"TAF7 (TAFII55) binds to the RAP74-binding domain of TAF1 (TAFII250) and inhibits its acetyltransferase (AT) activity; addition of recombinant TAF7 to in vitro transcription assays inhibits TAF1-dependent MHC class I transcription.","method":"Yeast two-hybrid screen, co-immunoprecipitation, in vitro acetyltransferase assay, in vitro transcription assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic assay with recombinant protein, functional transcription assay, replicated by subsequent studies","pmids":["11592977"],"is_preprint":false},{"year":2008,"finding":"TAF7 is released from TFIID upon transcription initiation and then interacts with TFIIH and P-TEFb, inhibiting their RNA Pol II CTD kinase activities; TAF7 inhibits transcription steps after PIC assembly and co-elongates with P-TEFb and Pol II downstream of the promoter in vivo.","method":"Co-immunoprecipitation, in vitro CTD kinase assay, in vitro transcription assay, chromatin immunoprecipitation (ChIP)","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase inhibition assay plus in vivo ChIP co-elongation, multiple orthogonal methods in single study","pmids":["18391197"],"is_preprint":false},{"year":2010,"finding":"TAF7 binds to the transcriptional co-activator CIITA and inhibits its acetyltransferase activity, thereby repressing CIITA-dependent MHC class I and II gene transcription; siRNA depletion of TAF7 increases CIITA-dependent transcription.","method":"Co-immunoprecipitation, in vitro acetyltransferase assay, siRNA knockdown with gene expression analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro enzymatic assay plus siRNA functional validation, multiple orthogonal methods","pmids":["20937824"],"is_preprint":false},{"year":2012,"finding":"TAF1 phosphorylates TAF7 at serine-264, disrupting the TAF1/TAF7 interaction within TFIID, which activates TAF1 HAT activity and increases histone H3 acetylation at the cyclin D1 and cyclin A promoters, stimulating their transcription; TAF7 S264A and S264D phosphomutants confirm the phosphorylation-dependent regulatory mechanism.","method":"Phosphorylation mapping, site-directed mutagenesis (S264A/S264D), overexpression, siRNA knockdown, ChIP for histone H3 acetylation","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — site-directed mutagenesis plus ChIP and functional transcription assays, multiple orthogonal methods in single study","pmids":["22711989"],"is_preprint":false},{"year":2014,"finding":"Crystal structure of the human TAF1 central core domain in complex with TAF7 reveals an inter-digitated compact architecture with a heterodimeric triple barrel and a TAF1 winged helix (WH) domain; the TAF1 WH domain has intrinsic DNA-binding activity dependent on characteristic WH residues, and mutation of these residues abrogates both DNA binding and rescue of the ts13 mutant phenotype.","method":"X-ray crystallography, DNA-binding assay, site-directed mutagenesis, cell-based rescue assay (ts13 mutant)","journal":"Cell research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus mutagenesis plus functional rescue assay, multiple orthogonal methods in single rigorous study","pmids":["25412659"],"is_preprint":false},{"year":2014,"finding":"Crystal structure of yeast TAF1-TAF7 complex at 2.9 Å shows a large hydrophobic heterodimer interface with extensive co-folding; one conserved surface pocket of the complex binds trimethylated histone H3K27 in a manner also regulated by phosphorylation at neighboring H3 serine, suggesting a role in reading epigenetic marks to regulate PIC assembly.","method":"X-ray crystallography, histone peptide binding assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus direct binding assay for histone mark recognition","pmids":["24927529"],"is_preprint":false},{"year":2012,"finding":"Germline TAF7 deletion is embryonic lethal between 3.5 and 5.5 days post-coitus; conditional deletion in mouse embryonic fibroblasts causes global cessation of transcription and cell proliferation arrest; TAF7 is essential for proliferation and differentiation of immature thymocytes but not for proliferation-independent differentiation of lineage-committed thymocytes; TAF7-deleted peripheral T cells cannot undergo activation and expansion.","method":"Conditional knockout mouse, embryonic lethality assessment, MEF transcription profiling, flow cytometry, T cell activation assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional KO in multiple cell types with defined phenotypic readouts, replicated across developmental stages","pmids":["22411629"],"is_preprint":false},{"year":1999,"finding":"Human TAF7 (TAFII55) interacts with the ligand-binding domains of the nuclear receptors VDR and TRα in a ligand-independent manner via a 40-amino-acid region spanning helices H3-H5; this interaction correlates with enhanced transcriptional activation in transfection experiments.","method":"Co-immunoprecipitation in COS cells, deletion mapping, transfection reporter assay, site-directed mutagenesis of RXR","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP in cells with deletion mapping and functional correlation, single lab","pmids":["10409738"],"is_preprint":false},{"year":2003,"finding":"TAF7 physically interacts with c-Jun through two independent interaction domains (N- and C-terminal parts of c-Jun), preferentially with DNA-bound phosphorylated c-Jun; increasing TAF7 levels enhances c-Jun transactivation in HEK293 and COS cells.","method":"GST pulldown, co-immunoprecipitation, transfection reporter assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — GST pulldown plus co-IP plus functional reporter assay, single lab","pmids":["12676957"],"is_preprint":false},{"year":2003,"finding":"TAF7L, a germ-cell-specific paralogue of TAF7, is tightly associated with TBP and interacts with TAF1 in pachytene and haploid spermatogenic cells, and its nuclear import coincides with decreased TAF7 expression, suggesting TAF7L replaces TAF7 as a TFIID subunit during spermatogenesis.","method":"Co-immunoprecipitation, immunofluorescence localization, western blotting across developmental stages","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — co-IP plus dynamic localization experiments, single lab, multiple methods","pmids":["12665565"],"is_preprint":false},{"year":2017,"finding":"The NTD of Mediator subunit MED26 interacts with a TAF7 peptide (residues 205-235) via the same groove (H3-H4 helices) that binds EAF1, with a Kd ~10 μM; NMR mapping shows TAF7 residues I222/F223 anchor a helix formed upon binding to a hydrophobic pocket of MED26-NTD, establishing a folding-upon-binding mechanism and a competitive switch between TAF7 and EAF1 binding during transcription initiation-to-elongation transition.","method":"NMR structure determination, NMR chemical shift perturbation mapping, isothermal titration calorimetry (Kd measurement), alanine mutagenesis","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structure with mutagenesis and binding affinity measurements, multiple orthogonal methods, single study","pmids":["28893534"],"is_preprint":false},{"year":2018,"finding":"TGF-β induces transcription of the ubiquitin ligase TRIM26, which ubiquitylates TAF7, targeting it for proteasomal degradation; this TAF7 degradation is required for TGF-β-induced proliferative arrest in mouse mammary epithelial cells. MYC inhibits TRIM26 induction by TGF-β, antagonizing TAF7 degradation.","method":"Co-immunoprecipitation, ubiquitylation assay, proteasome inhibitor rescue, siRNA knockdown, Myc amplification analysis","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ubiquitylation assay plus functional proliferation phenotype, single lab, multiple methods","pmids":["29203640"],"is_preprint":false},{"year":2018,"finding":"TAF7 is a phosphoprotein whose phosphorylation status regulates both its interaction with TFIID and its stability via the ubiquitin-proteasome pathway; heat shock induces HSF1-driven TAF7 expression; TAF7 is required for sustained expression of heat shock protein genes and binds the HSP gene promoter during prolonged transcription, enhancing Pol II levels at the gene body to facilitate initiation-to-elongation transition.","method":"ChIP, RT-qPCR, western blotting, phosphorylation analysis, ubiquitin-proteasome pathway inhibition","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — ChIP with functional gene expression analysis, single lab, multiple methods","pmids":["30028080"],"is_preprint":false},{"year":2021,"finding":"TAF7 binds RNAs in the nucleus through consensus CUG motifs within 3′ UTRs (including the HIV-1 TAR element) and exports them to cytoplasmic polysomes via a nuclear export signal dependent on exportin 1 (CRM1); disruption of TAF7 RNA binding or nuclear export retains target mRNAs in the nucleus and reduces levels of their protein products.","method":"RNA immunoprecipitation, CLIP-seq, nuclear/cytoplasmic fractionation, polysome profiling, exportin 1 inhibition (leptomycin B), mutagenesis of NES and RNA-binding motifs","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — CLIP-seq plus fractionation plus polysome profiling plus mutagenesis, multiple orthogonal methods in single study","pmids":["34890234"],"is_preprint":false},{"year":2024,"finding":"SETD7 methyltransferase methylates TAF7 at lysine residues K5 and K300, resulting in TAF7 deubiquitination and protein stabilization; methylated TAF7 shows higher transcriptional activity at the CCNA2 (cyclin A2) promoter compared to unmethylated TAF7.","method":"Co-immunoprecipitation, site-directed mutagenesis (K5/K300), in vitro methylation assay, ubiquitination assay, ChIP, reporter assay","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro methylation assay plus mutagenesis plus functional transcription readout, single lab","pmids":["38904013"],"is_preprint":false},{"year":2025,"finding":"TAF7 binds to a specific motif in the SAA1 gene promoter and enhances SAA1 transcription; elevated SAA1 promotes TNBC cell invasion and migration by increasing E-cadherin and N-cadherin phosphorylation, and TAF7 modulates lung metastasis through an SAA1-dependent mechanism in vitro and in vivo.","method":"ChIP, knockdown/overexpression, reporter assay, invasion/migration assays, mouse xenograft metastasis model","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — ChIP plus functional in vivo and in vitro assays, single lab","pmids":["40083715"],"is_preprint":false},{"year":1997,"finding":"YY1 binds to TAFII55 (TAF7) through its zinc finger and Gly/Ala-rich domains (not its transactivation domain), indicating this interaction may be involved in repression or transcription initiation rather than transactivation.","method":"Co-immunoprecipitation, deletion mutagenesis, transcription reporter assay","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP with partial mechanistic mapping, single lab, no functional follow-up on the TAF7 interaction specifically","pmids":["8999850"],"is_preprint":false}],"current_model":"TAF7 is a multifunctional TFIID subunit that acts as a checkpoint regulator of transcription initiation by binding TAF1 (TAFII250) and inhibiting its acetyltransferase activity (relieved when TAF1 phosphorylates TAF7 at S264), interacts with and inhibits the CTD kinase activities of TFIIH and P-TEFb to gate the transition from PIC assembly to elongation, inhibits CIITA acetyltransferase activity to repress TAF1-independent transcription, is structurally organized as a compact heterodimer with TAF1 featuring a DNA-binding winged helix domain and a histone H3K27me3-reading pocket, is targeted for proteasomal degradation by the TRIM26 ubiquitin ligase downstream of TGF-β signaling, is methylated and stabilized by SETD7, and additionally functions as a cytoplasmic RNA chaperone that exports target mRNAs from the nucleus to polysomes via an exportin 1-dependent pathway."},"narrative":{"mechanistic_narrative":"TAF7 is a TFIID subunit that functions as a checkpoint regulator gating the transition from preinitiation complex (PIC) assembly to productive transcription elongation [PMID:18391197]. Within TFIID, TAF7 binds the RAP74-binding domain of TAF1 (TAFII250) and inhibits its acetyltransferase activity, holding the complex in a repressed state [PMID:11592977]; this restraint is relieved when TAF1 phosphorylates TAF7 at serine-264, disrupting the TAF1/TAF7 interaction, activating TAF1 HAT activity and promoting histone H3 acetylation and transcription at cyclin D1 and cyclin A promoters [PMID:22711989]. Structural work shows TAF7 and TAF1 co-fold into a compact, inter-digitated heterodimer bearing a TAF1 winged-helix DNA-binding domain and a conserved pocket that reads trimethylated histone H3K27, coupling epigenetic mark recognition to PIC regulation [PMID:25412659, PMID:24927529]. Upon initiation, TAF7 is released from TFIID and inhibits the RNA Pol II CTD kinase activities of TFIIH and P-TEFb, co-elongating with Pol II downstream of the promoter [PMID:18391197], with a competitive folding-upon-binding switch on the MED26 N-terminal domain marking the initiation-to-elongation handoff [PMID:28893534]. TAF7 also inhibits the acetyltransferase activity of the coactivator CIITA to repress MHC gene transcription [PMID:20937824], and is essential for global transcription, proliferation, and T-cell development in vivo [PMID:22411629]. TAF7 abundance is controlled post-translationally: TGF-β-induced TRIM26 ubiquitylates TAF7 for proteasomal degradation to enforce proliferative arrest [PMID:29203640], while SETD7 methylation deubiquitinates and stabilizes TAF7 to enhance its activity at the cyclin A2 promoter [PMID:38904013]. Beyond transcription, TAF7 acts as a cytoplasmic RNA chaperone, binding CUG-motif-containing 3' UTRs and exporting target mRNAs to polysomes through an exportin 1 (CRM1)-dependent nuclear export signal [PMID:34890234].","teleology":[{"year":1997,"claim":"An early question was whether TAF7 contacts sequence-specific factors beyond the basal machinery; YY1 was found to bind TAF7, hinting at a role in repression or initiation rather than transactivation.","evidence":"Co-immunoprecipitation and deletion mutagenesis with reporter assays","pmids":["8999850"],"confidence":"Low","gaps":["Single co-IP with no functional follow-up specific to the TAF7 interaction","Domain mapping of the binding interface incomplete"]},{"year":1999,"claim":"To test whether TAF7 links TFIID to ligand-activated transcription, it was shown to bind nuclear receptor ligand-binding domains independent of ligand and correlate with enhanced activation.","evidence":"Co-IP in COS cells, deletion mapping, reporter assays","pmids":["10409738"],"confidence":"Medium","gaps":["Functional link is correlative","Single lab, no in vivo validation"]},{"year":2001,"claim":"The first defined biochemical activity of TAF7 was established: it binds the TAF1 RAP74-binding domain and inhibits TAF1 acetyltransferase activity, repressing TAF1-dependent transcription.","evidence":"Yeast two-hybrid, co-IP, in vitro acetyltransferase and transcription assays","pmids":["11592977"],"confidence":"High","gaps":["How inhibition is relieved was not defined","Structural basis of the interaction unknown at this stage"]},{"year":2003,"claim":"TAF7 interactions with sequence-specific activators were extended to c-Jun, indicating TAF7 can engage DNA-bound phosphorylated transcription factors to modulate their activity.","evidence":"GST pulldown, co-IP, reporter assays in HEK293/COS cells","pmids":["12676957"],"confidence":"Medium","gaps":["Mechanism of transactivation enhancement undefined","No endogenous-gene validation"]},{"year":2003,"claim":"A germ-cell-specific paralogue (TAF7L) was shown to associate with TBP/TAF1 and replace TAF7 during spermatogenesis, establishing tissue-specific TFIID remodeling around the TAF7 slot.","evidence":"Co-IP, immunofluorescence, staged western blotting","pmids":["12665565"],"confidence":"Medium","gaps":["Functional consequences of the swap not directly tested","Concerns paralogue rather than TAF7 itself"]},{"year":2008,"claim":"The checkpoint model emerged: TAF7 is released from TFIID at initiation and then inhibits the CTD kinases of TFIIH and P-TEFb, gating the step after PIC assembly while co-elongating with Pol II.","evidence":"Co-IP, in vitro CTD kinase and transcription assays, ChIP co-elongation in vivo","pmids":["18391197"],"confidence":"High","gaps":["Trigger for TAF7 release from TFIID not defined","Structural basis of kinase inhibition unknown"]},{"year":2010,"claim":"TAF7's inhibitory acetyltransferase regulation was generalized beyond TAF1: it binds and inhibits CIITA AT activity to repress TAF1-independent MHC transcription.","evidence":"Co-IP, in vitro acetyltransferase assay, siRNA with expression analysis","pmids":["20937824"],"confidence":"High","gaps":["Structural mode of CIITA inhibition unknown","Physiological contexts not mapped"]},{"year":2012,"claim":"The relief mechanism for TAF1 inhibition was defined: TAF1 phosphorylates TAF7 at S264, disrupting the heterodimer, activating TAF1 HAT and driving cyclin promoter transcription.","evidence":"Phospho-mapping, S264A/S264D mutants, ChIP for H3 acetylation, knockdown","pmids":["22711989"],"confidence":"High","gaps":["Upstream signals controlling TAF1 kinase activity unclear","Generality beyond cyclin promoters not established"]},{"year":2012,"claim":"Genetic essentiality was established: germline TAF7 loss is embryonic lethal and conditional deletion abolishes transcription and proliferation, including immature thymocyte and T-cell expansion.","evidence":"Conditional knockout mouse, MEF profiling, flow cytometry, T-cell activation assays","pmids":["22411629"],"confidence":"High","gaps":["Distinguishes proliferation-dependent from -independent programs but mechanism of selectivity unresolved","Cell-type-specific target genes not catalogued"]},{"year":2014,"claim":"Crystal structures of the TAF1-TAF7 core revealed an inter-digitated heterodimer with a DNA-binding winged-helix domain and an H3K27me3-reading pocket, providing the structural basis for chromatin-coupled PIC regulation.","evidence":"X-ray crystallography (human and yeast complexes), DNA/histone-peptide binding, mutagenesis, ts13 rescue","pmids":["25412659","24927529"],"confidence":"High","gaps":["How H3K27me3 reading feeds into transcriptional output in vivo not shown","Conformational changes during TAF7 release not captured"]},{"year":2017,"claim":"The initiation-to-elongation handoff was given a structural switch: TAF7 folds upon binding the MED26 NTD groove in competition with EAF1, coupling Mediator engagement to transition control.","evidence":"NMR structure, chemical-shift mapping, ITC (Kd ~10 µM), alanine mutagenesis","pmids":["28893534"],"confidence":"High","gaps":["In vivo relevance of the TAF7/EAF1 competition not demonstrated","Temporal ordering relative to CTD-kinase inhibition unresolved"]},{"year":2018,"claim":"Post-translational control of TAF7 abundance was uncovered: TGF-β-induced TRIM26 ubiquitylates TAF7 for degradation to enforce proliferative arrest, antagonized by MYC.","evidence":"Co-IP, ubiquitylation assay, proteasome rescue, siRNA, MYC amplification analysis","pmids":["29203640"],"confidence":"Medium","gaps":["Direct ubiquitylation sites on TAF7 not mapped","Single lab"]},{"year":2018,"claim":"TAF7 phosphorylation was tied to both TFIID interaction and proteasomal stability, and TAF7 was shown to sustain heat-shock gene expression by enhancing Pol II at gene bodies during prolonged transcription.","evidence":"ChIP, RT-qPCR, western blotting, phospho-analysis, proteasome inhibition","pmids":["30028080"],"confidence":"Medium","gaps":["Specific phospho-residues governing stability not defined","Mechanism of Pol II body enrichment unresolved"]},{"year":2021,"claim":"A non-transcriptional function was established: TAF7 binds CUG-motif 3' UTR RNAs and exports them to polysomes via an exportin 1-dependent NES, acting as a cytoplasmic RNA chaperone.","evidence":"RNA-IP, CLIP-seq, fractionation, polysome profiling, leptomycin B, NES/RNA-motif mutagenesis","pmids":["34890234"],"confidence":"High","gaps":["Relationship between RNA-export and TFIID roles not integrated","Structural basis of RNA recognition unknown"]},{"year":2024,"claim":"A stabilizing modification was added to the regulatory repertoire: SETD7 methylates TAF7 at K5/K300, causing deubiquitination, stabilization, and increased activity at the cyclin A2 promoter.","evidence":"In vitro methylation, K5/K300 mutagenesis, ubiquitination assay, ChIP, reporter assays","pmids":["38904013"],"confidence":"Medium","gaps":["Crosstalk with TRIM26-mediated degradation not tested","Single lab"]},{"year":2025,"claim":"TAF7 was linked to disease physiology: it directly activates SAA1 transcription to drive TNBC cell invasion and lung metastasis.","evidence":"ChIP, knockdown/overexpression, reporter, invasion/migration assays, xenograft metastasis model","pmids":["40083715"],"confidence":"Medium","gaps":["Whether this reflects TFIID or RNA-chaperone activity unclear","Single lab"]},{"year":null,"claim":"How TAF7's distinct activities — TFIID-resident HAT inhibition, CTD-kinase gating, chromatin-mark reading, and cytoplasmic mRNA export — are coordinated within one cell and which signals partition TAF7 between them remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking nuclear transcriptional and cytoplasmic RNA-export functions","Signal-dependent switching between activities uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,2,3,15]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[13]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[4]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[5]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[13]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,3,13]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[13]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[3,5]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,3]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[3,5]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[13]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2,6]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,6,14]}],"complexes":["TFIID"],"partners":["TAF1","CIITA","MED26","TRIM26","SETD7","VDR","JUN","YY1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15545","full_name":"Transcription initiation factor TFIID subunit 7","aliases":["RNA polymerase II TBP-associated factor subunit F","Transcription initiation factor TFIID 55 kDa subunit","TAF(II)55","TAFII-55","TAFII55"],"length_aa":349,"mass_kda":40.3,"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:10438527, PubMed:33795473). TAF7 forms a promoter DNA binding subcomplex of TFIID, together with TAF1 and TAF2 (PubMed:33795473). Part of a TFIID complex containing TAF10 (TFIID alpha) and a TFIID complex lacking TAF10 (TFIID beta) (PubMed:10438527)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q15545/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TAF7","classification":"Common Essential","n_dependent_lines":1155,"n_total_lines":1208,"dependency_fraction":0.9561258278145696},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TBP","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/search/TAF7","total_profiled":1310},"omim":[{"mim_id":"601930","title":"BASONUCLIN 1; BNC1","url":"https://www.omim.org/entry/601930"},{"mim_id":"600573","title":"TAF7 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 55-KD; TAF7","url":"https://www.omim.org/entry/600573"},{"mim_id":"313650","title":"TAF1 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 250-KD; TAF1","url":"https://www.omim.org/entry/313650"},{"mim_id":"300966","title":"INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 33; MRXS33","url":"https://www.omim.org/entry/300966"},{"mim_id":"300314","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 7-LIKE; TAF7L","url":"https://www.omim.org/entry/300314"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAF7"},"hgnc":{"alias_symbol":["TAFII55"],"prev_symbol":["TAF2F"]},"alphafold":{"accession":"Q15545","domains":[{"cath_id":"-","chopping":"16-106_116-146","consensus_level":"high","plddt":90.823,"start":16,"end":146},{"cath_id":"1.20.58","chopping":"275-347","consensus_level":"high","plddt":90.5148,"start":275,"end":347}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15545","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15545-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15545-F1-predicted_aligned_error_v6.png","plddt_mean":76.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAF7","jax_strain_url":"https://www.jax.org/strain/search?query=TAF7"},"sequence":{"accession":"Q15545","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15545.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15545/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15545"}},"corpus_meta":[{"pmid":"8999850","id":"PMC_8999850","title":"Characterization of the transcriptional regulator YY1. The bipartite transactivation domain is independent of interaction with the TATA box-binding protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding protein (CPB)-binding protein.","date":"1997","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8999850","citation_count":185,"is_preprint":false},{"pmid":"12665565","id":"PMC_12665565","title":"The intracellular localisation of TAF7L, a paralogue of transcription factor TFIID subunit TAF7, is developmentally regulated during male germ-cell differentiation.","date":"2003","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/12665565","citation_count":100,"is_preprint":false},{"pmid":"25412659","id":"PMC_25412659","title":"Crystal structure of a TAF1-TAF7 complex in human transcription factor IID reveals a promoter binding module.","date":"2014","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/25412659","citation_count":48,"is_preprint":false},{"pmid":"11340078","id":"PMC_11340078","title":"The intronless and TATA-less human TAF(II)55 gene contains a functional initiator and a downstream promoter element.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11340078","citation_count":47,"is_preprint":false},{"pmid":"24927529","id":"PMC_24927529","title":"Structural and functional insight into TAF1-TAF7, a subcomplex of transcription factor II D.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24927529","citation_count":42,"is_preprint":false},{"pmid":"22411629","id":"PMC_22411629","title":"The general transcription factor TAF7 is essential for embryonic development but not essential for the survival or differentiation of mature T cells.","date":"2012","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22411629","citation_count":41,"is_preprint":false},{"pmid":"11592977","id":"PMC_11592977","title":"TAFII55 binding to TAFII250 inhibits its acetyltransferase activity.","date":"2001","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11592977","citation_count":39,"is_preprint":false},{"pmid":"10409738","id":"PMC_10409738","title":"Human TAF(II)55 interacts with the vitamin D(3) and thyroid hormone receptors and with derivatives of the retinoid X receptor that have altered transactivation properties.","date":"1999","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10409738","citation_count":38,"is_preprint":false},{"pmid":"18391197","id":"PMC_18391197","title":"TFIID component TAF7 functionally interacts with both TFIIH and P-TEFb.","date":"2008","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/18391197","citation_count":34,"is_preprint":false},{"pmid":"22711989","id":"PMC_22711989","title":"Phosphorylation-dependent regulation of cyclin D1 and cyclin A gene transcription by TFIID subunits TAF1 and TAF7.","date":"2012","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22711989","citation_count":33,"is_preprint":false},{"pmid":"12364593","id":"PMC_12364593","title":"Sp1 and AP2 regulate but do not constitute TATA-less human TAF(II)55 core promoter activity.","date":"2002","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/12364593","citation_count":27,"is_preprint":false},{"pmid":"12676957","id":"PMC_12676957","title":"TAF7 (TAFII55) plays a role in the transcription activation by c-Jun.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12676957","citation_count":24,"is_preprint":false},{"pmid":"20937824","id":"PMC_20937824","title":"Novel functions for TAF7, a regulator of TAF1-independent transcription.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20937824","citation_count":21,"is_preprint":false},{"pmid":"23340207","id":"PMC_23340207","title":"TAF7: traffic controller in transcription initiation.","date":"2013","source":"Transcription","url":"https://pubmed.ncbi.nlm.nih.gov/23340207","citation_count":19,"is_preprint":false},{"pmid":"34890234","id":"PMC_34890234","title":"The nuclear transcription factor, TAF7, is a cytoplasmic regulator of protein synthesis.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/34890234","citation_count":17,"is_preprint":false},{"pmid":"28893534","id":"PMC_28893534","title":"Solution Structure of the N-Terminal Domain of Mediator Subunit MED26 and Molecular Characterization of Its Interaction with EAF1 and TAF7.","date":"2017","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/28893534","citation_count":12,"is_preprint":false},{"pmid":"29203640","id":"PMC_29203640","title":"Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC.","date":"2018","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/29203640","citation_count":12,"is_preprint":false},{"pmid":"38904013","id":"PMC_38904013","title":"SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma.","date":"2024","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38904013","citation_count":9,"is_preprint":false},{"pmid":"30028080","id":"PMC_30028080","title":"TAF7 is a heat-inducible unstable protein and is required for sustained expression of heat shock protein genes.","date":"2018","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/30028080","citation_count":6,"is_preprint":false},{"pmid":"34762273","id":"PMC_34762273","title":"Novel variations in spermatogenic transcription regulators RFX2 and TAF7 increase risk of azoospermia.","date":"2021","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34762273","citation_count":5,"is_preprint":false},{"pmid":"39457533","id":"PMC_39457533","title":"Busulfan Chemotherapy Downregulates TAF7/TNF-α Signaling in Male Germ Cell Dysfunction.","date":"2024","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/39457533","citation_count":3,"is_preprint":false},{"pmid":"40083715","id":"PMC_40083715","title":"TAF7 directly targets SAA1 to enhance triple-negative breast cancer metastasis via phosphorylating E-cadherin and 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assay, in vitro transcription assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic assay with recombinant protein, functional transcription assay, replicated by subsequent studies\",\n      \"pmids\": [\"11592977\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"TAF7 is released from TFIID upon transcription initiation and then interacts with TFIIH and P-TEFb, inhibiting their RNA Pol II CTD kinase activities; TAF7 inhibits transcription steps after PIC assembly and co-elongates with P-TEFb and Pol II downstream of the promoter in vivo.\",\n      \"method\": \"Co-immunoprecipitation, in vitro CTD kinase assay, in vitro transcription assay, chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase inhibition assay plus in vivo ChIP co-elongation, multiple orthogonal methods in single study\",\n      \"pmids\": [\"18391197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"TAF7 binds to the transcriptional co-activator CIITA and inhibits its acetyltransferase activity, thereby repressing CIITA-dependent MHC class I and II gene transcription; siRNA depletion of TAF7 increases CIITA-dependent transcription.\",\n      \"method\": \"Co-immunoprecipitation, in vitro acetyltransferase assay, siRNA knockdown with gene expression analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro enzymatic assay plus siRNA functional validation, multiple orthogonal methods\",\n      \"pmids\": [\"20937824\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"TAF1 phosphorylates TAF7 at serine-264, disrupting the TAF1/TAF7 interaction within TFIID, which activates TAF1 HAT activity and increases histone H3 acetylation at the cyclin D1 and cyclin A promoters, stimulating their transcription; TAF7 S264A and S264D phosphomutants confirm the phosphorylation-dependent regulatory mechanism.\",\n      \"method\": \"Phosphorylation mapping, site-directed mutagenesis (S264A/S264D), overexpression, siRNA knockdown, ChIP for histone H3 acetylation\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — site-directed mutagenesis plus ChIP and functional transcription assays, multiple orthogonal methods in single study\",\n      \"pmids\": [\"22711989\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Crystal structure of the human TAF1 central core domain in complex with TAF7 reveals an inter-digitated compact architecture with a heterodimeric triple barrel and a TAF1 winged helix (WH) domain; the TAF1 WH domain has intrinsic DNA-binding activity dependent on characteristic WH residues, and mutation of these residues abrogates both DNA binding and rescue of the ts13 mutant phenotype.\",\n      \"method\": \"X-ray crystallography, DNA-binding assay, site-directed mutagenesis, cell-based rescue assay (ts13 mutant)\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus mutagenesis plus functional rescue assay, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"25412659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Crystal structure of yeast TAF1-TAF7 complex at 2.9 Å shows a large hydrophobic heterodimer interface with extensive co-folding; one conserved surface pocket of the complex binds trimethylated histone H3K27 in a manner also regulated by phosphorylation at neighboring H3 serine, suggesting a role in reading epigenetic marks to regulate PIC assembly.\",\n      \"method\": \"X-ray crystallography, histone peptide binding assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus direct binding assay for histone mark recognition\",\n      \"pmids\": [\"24927529\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Germline TAF7 deletion is embryonic lethal between 3.5 and 5.5 days post-coitus; conditional deletion in mouse embryonic fibroblasts causes global cessation of transcription and cell proliferation arrest; TAF7 is essential for proliferation and differentiation of immature thymocytes but not for proliferation-independent differentiation of lineage-committed thymocytes; TAF7-deleted peripheral T cells cannot undergo activation and expansion.\",\n      \"method\": \"Conditional knockout mouse, embryonic lethality assessment, MEF transcription profiling, flow cytometry, T cell activation assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional KO in multiple cell types with defined phenotypic readouts, replicated across developmental stages\",\n      \"pmids\": [\"22411629\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Human TAF7 (TAFII55) interacts with the ligand-binding domains of the nuclear receptors VDR and TRα in a ligand-independent manner via a 40-amino-acid region spanning helices H3-H5; this interaction correlates with enhanced transcriptional activation in transfection experiments.\",\n      \"method\": \"Co-immunoprecipitation in COS cells, deletion mapping, transfection reporter assay, site-directed mutagenesis of RXR\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP in cells with deletion mapping and functional correlation, single lab\",\n      \"pmids\": [\"10409738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TAF7 physically interacts with c-Jun through two independent interaction domains (N- and C-terminal parts of c-Jun), preferentially with DNA-bound phosphorylated c-Jun; increasing TAF7 levels enhances c-Jun transactivation in HEK293 and COS cells.\",\n      \"method\": \"GST pulldown, co-immunoprecipitation, transfection reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — GST pulldown plus co-IP plus functional reporter assay, single lab\",\n      \"pmids\": [\"12676957\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TAF7L, a germ-cell-specific paralogue of TAF7, is tightly associated with TBP and interacts with TAF1 in pachytene and haploid spermatogenic cells, and its nuclear import coincides with decreased TAF7 expression, suggesting TAF7L replaces TAF7 as a TFIID subunit during spermatogenesis.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence localization, western blotting across developmental stages\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — co-IP plus dynamic localization experiments, single lab, multiple methods\",\n      \"pmids\": [\"12665565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The NTD of Mediator subunit MED26 interacts with a TAF7 peptide (residues 205-235) via the same groove (H3-H4 helices) that binds EAF1, with a Kd ~10 μM; NMR mapping shows TAF7 residues I222/F223 anchor a helix formed upon binding to a hydrophobic pocket of MED26-NTD, establishing a folding-upon-binding mechanism and a competitive switch between TAF7 and EAF1 binding during transcription initiation-to-elongation transition.\",\n      \"method\": \"NMR structure determination, NMR chemical shift perturbation mapping, isothermal titration calorimetry (Kd measurement), alanine mutagenesis\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structure with mutagenesis and binding affinity measurements, multiple orthogonal methods, single study\",\n      \"pmids\": [\"28893534\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TGF-β induces transcription of the ubiquitin ligase TRIM26, which ubiquitylates TAF7, targeting it for proteasomal degradation; this TAF7 degradation is required for TGF-β-induced proliferative arrest in mouse mammary epithelial cells. MYC inhibits TRIM26 induction by TGF-β, antagonizing TAF7 degradation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation assay, proteasome inhibitor rescue, siRNA knockdown, Myc amplification analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ubiquitylation assay plus functional proliferation phenotype, single lab, multiple methods\",\n      \"pmids\": [\"29203640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TAF7 is a phosphoprotein whose phosphorylation status regulates both its interaction with TFIID and its stability via the ubiquitin-proteasome pathway; heat shock induces HSF1-driven TAF7 expression; TAF7 is required for sustained expression of heat shock protein genes and binds the HSP gene promoter during prolonged transcription, enhancing Pol II levels at the gene body to facilitate initiation-to-elongation transition.\",\n      \"method\": \"ChIP, RT-qPCR, western blotting, phosphorylation analysis, ubiquitin-proteasome pathway inhibition\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — ChIP with functional gene expression analysis, single lab, multiple methods\",\n      \"pmids\": [\"30028080\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TAF7 binds RNAs in the nucleus through consensus CUG motifs within 3′ UTRs (including the HIV-1 TAR element) and exports them to cytoplasmic polysomes via a nuclear export signal dependent on exportin 1 (CRM1); disruption of TAF7 RNA binding or nuclear export retains target mRNAs in the nucleus and reduces levels of their protein products.\",\n      \"method\": \"RNA immunoprecipitation, CLIP-seq, nuclear/cytoplasmic fractionation, polysome profiling, exportin 1 inhibition (leptomycin B), mutagenesis of NES and RNA-binding motifs\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — CLIP-seq plus fractionation plus polysome profiling plus mutagenesis, multiple orthogonal methods in single study\",\n      \"pmids\": [\"34890234\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SETD7 methyltransferase methylates TAF7 at lysine residues K5 and K300, resulting in TAF7 deubiquitination and protein stabilization; methylated TAF7 shows higher transcriptional activity at the CCNA2 (cyclin A2) promoter compared to unmethylated TAF7.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis (K5/K300), in vitro methylation assay, ubiquitination assay, ChIP, reporter assay\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro methylation assay plus mutagenesis plus functional transcription readout, single lab\",\n      \"pmids\": [\"38904013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TAF7 binds to a specific motif in the SAA1 gene promoter and enhances SAA1 transcription; elevated SAA1 promotes TNBC cell invasion and migration by increasing E-cadherin and N-cadherin phosphorylation, and TAF7 modulates lung metastasis through an SAA1-dependent mechanism in vitro and in vivo.\",\n      \"method\": \"ChIP, knockdown/overexpression, reporter assay, invasion/migration assays, mouse xenograft metastasis model\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — ChIP plus functional in vivo and in vitro assays, single lab\",\n      \"pmids\": [\"40083715\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"YY1 binds to TAFII55 (TAF7) through its zinc finger and Gly/Ala-rich domains (not its transactivation domain), indicating this interaction may be involved in repression or transcription initiation rather than transactivation.\",\n      \"method\": \"Co-immunoprecipitation, deletion mutagenesis, transcription reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP with partial mechanistic mapping, single lab, no functional follow-up on the TAF7 interaction specifically\",\n      \"pmids\": [\"8999850\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAF7 is a multifunctional TFIID subunit that acts as a checkpoint regulator of transcription initiation by binding TAF1 (TAFII250) and inhibiting its acetyltransferase activity (relieved when TAF1 phosphorylates TAF7 at S264), interacts with and inhibits the CTD kinase activities of TFIIH and P-TEFb to gate the transition from PIC assembly to elongation, inhibits CIITA acetyltransferase activity to repress TAF1-independent transcription, is structurally organized as a compact heterodimer with TAF1 featuring a DNA-binding winged helix domain and a histone H3K27me3-reading pocket, is targeted for proteasomal degradation by the TRIM26 ubiquitin ligase downstream of TGF-β signaling, is methylated and stabilized by SETD7, and additionally functions as a cytoplasmic RNA chaperone that exports target mRNAs from the nucleus to polysomes via an exportin 1-dependent pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TAF7 is a TFIID subunit that functions as a checkpoint regulator gating the transition from preinitiation complex (PIC) assembly to productive transcription elongation [#1]. Within TFIID, TAF7 binds the RAP74-binding domain of TAF1 (TAFII250) and inhibits its acetyltransferase activity, holding the complex in a repressed state [#0]; this restraint is relieved when TAF1 phosphorylates TAF7 at serine-264, disrupting the TAF1/TAF7 interaction, activating TAF1 HAT activity and promoting histone H3 acetylation and transcription at cyclin D1 and cyclin A promoters [#3]. Structural work shows TAF7 and TAF1 co-fold into a compact, inter-digitated heterodimer bearing a TAF1 winged-helix DNA-binding domain and a conserved pocket that reads trimethylated histone H3K27, coupling epigenetic mark recognition to PIC regulation [#4, #5]. Upon initiation, TAF7 is released from TFIID and inhibits the RNA Pol II CTD kinase activities of TFIIH and P-TEFb, co-elongating with Pol II downstream of the promoter [#1], with a competitive folding-upon-binding switch on the MED26 N-terminal domain marking the initiation-to-elongation handoff [#10]. TAF7 also inhibits the acetyltransferase activity of the coactivator CIITA to repress MHC gene transcription [#2], and is essential for global transcription, proliferation, and T-cell development in vivo [#6]. TAF7 abundance is controlled post-translationally: TGF-\\u03b2-induced TRIM26 ubiquitylates TAF7 for proteasomal degradation to enforce proliferative arrest [#11], while SETD7 methylation deubiquitinates and stabilizes TAF7 to enhance its activity at the cyclin A2 promoter [#14]. Beyond transcription, TAF7 acts as a cytoplasmic RNA chaperone, binding CUG-motif-containing 3' UTRs and exporting target mRNAs to polysomes through an exportin 1 (CRM1)-dependent nuclear export signal [#13].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"An early question was whether TAF7 contacts sequence-specific factors beyond the basal machinery; YY1 was found to bind TAF7, hinting at a role in repression or initiation rather than transactivation.\",\n      \"evidence\": \"Co-immunoprecipitation and deletion mutagenesis with reporter assays\",\n      \"pmids\": [\"8999850\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single co-IP with no functional follow-up specific to the TAF7 interaction\", \"Domain mapping of the binding interface incomplete\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"To test whether TAF7 links TFIID to ligand-activated transcription, it was shown to bind nuclear receptor ligand-binding domains independent of ligand and correlate with enhanced activation.\",\n      \"evidence\": \"Co-IP in COS cells, deletion mapping, reporter assays\",\n      \"pmids\": [\"10409738\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional link is correlative\", \"Single lab, no in vivo validation\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"The first defined biochemical activity of TAF7 was established: it binds the TAF1 RAP74-binding domain and inhibits TAF1 acetyltransferase activity, repressing TAF1-dependent transcription.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP, in vitro acetyltransferase and transcription assays\",\n      \"pmids\": [\"11592977\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How inhibition is relieved was not defined\", \"Structural basis of the interaction unknown at this stage\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"TAF7 interactions with sequence-specific activators were extended to c-Jun, indicating TAF7 can engage DNA-bound phosphorylated transcription factors to modulate their activity.\",\n      \"evidence\": \"GST pulldown, co-IP, reporter assays in HEK293/COS cells\",\n      \"pmids\": [\"12676957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of transactivation enhancement undefined\", \"No endogenous-gene validation\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"A germ-cell-specific paralogue (TAF7L) was shown to associate with TBP/TAF1 and replace TAF7 during spermatogenesis, establishing tissue-specific TFIID remodeling around the TAF7 slot.\",\n      \"evidence\": \"Co-IP, immunofluorescence, staged western blotting\",\n      \"pmids\": [\"12665565\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequences of the swap not directly tested\", \"Concerns paralogue rather than TAF7 itself\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"The checkpoint model emerged: TAF7 is released from TFIID at initiation and then inhibits the CTD kinases of TFIIH and P-TEFb, gating the step after PIC assembly while co-elongating with Pol II.\",\n      \"evidence\": \"Co-IP, in vitro CTD kinase and transcription assays, ChIP co-elongation in vivo\",\n      \"pmids\": [\"18391197\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger for TAF7 release from TFIID not defined\", \"Structural basis of kinase inhibition unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"TAF7's inhibitory acetyltransferase regulation was generalized beyond TAF1: it binds and inhibits CIITA AT activity to repress TAF1-independent MHC transcription.\",\n      \"evidence\": \"Co-IP, in vitro acetyltransferase assay, siRNA with expression analysis\",\n      \"pmids\": [\"20937824\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural mode of CIITA inhibition unknown\", \"Physiological contexts not mapped\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The relief mechanism for TAF1 inhibition was defined: TAF1 phosphorylates TAF7 at S264, disrupting the heterodimer, activating TAF1 HAT and driving cyclin promoter transcription.\",\n      \"evidence\": \"Phospho-mapping, S264A/S264D mutants, ChIP for H3 acetylation, knockdown\",\n      \"pmids\": [\"22711989\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream signals controlling TAF1 kinase activity unclear\", \"Generality beyond cyclin promoters not established\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Genetic essentiality was established: germline TAF7 loss is embryonic lethal and conditional deletion abolishes transcription and proliferation, including immature thymocyte and T-cell expansion.\",\n      \"evidence\": \"Conditional knockout mouse, MEF profiling, flow cytometry, T-cell activation assays\",\n      \"pmids\": [\"22411629\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Distinguishes proliferation-dependent from -independent programs but mechanism of selectivity unresolved\", \"Cell-type-specific target genes not catalogued\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Crystal structures of the TAF1-TAF7 core revealed an inter-digitated heterodimer with a DNA-binding winged-helix domain and an H3K27me3-reading pocket, providing the structural basis for chromatin-coupled PIC regulation.\",\n      \"evidence\": \"X-ray crystallography (human and yeast complexes), DNA/histone-peptide binding, mutagenesis, ts13 rescue\",\n      \"pmids\": [\"25412659\", \"24927529\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How H3K27me3 reading feeds into transcriptional output in vivo not shown\", \"Conformational changes during TAF7 release not captured\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The initiation-to-elongation handoff was given a structural switch: TAF7 folds upon binding the MED26 NTD groove in competition with EAF1, coupling Mediator engagement to transition control.\",\n      \"evidence\": \"NMR structure, chemical-shift mapping, ITC (Kd ~10 \\u00b5M), alanine mutagenesis\",\n      \"pmids\": [\"28893534\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo relevance of the TAF7/EAF1 competition not demonstrated\", \"Temporal ordering relative to CTD-kinase inhibition unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Post-translational control of TAF7 abundance was uncovered: TGF-\\u03b2-induced TRIM26 ubiquitylates TAF7 for degradation to enforce proliferative arrest, antagonized by MYC.\",\n      \"evidence\": \"Co-IP, ubiquitylation assay, proteasome rescue, siRNA, MYC amplification analysis\",\n      \"pmids\": [\"29203640\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct ubiquitylation sites on TAF7 not mapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"TAF7 phosphorylation was tied to both TFIID interaction and proteasomal stability, and TAF7 was shown to sustain heat-shock gene expression by enhancing Pol II at gene bodies during prolonged transcription.\",\n      \"evidence\": \"ChIP, RT-qPCR, western blotting, phospho-analysis, proteasome inhibition\",\n      \"pmids\": [\"30028080\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific phospho-residues governing stability not defined\", \"Mechanism of Pol II body enrichment unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A non-transcriptional function was established: TAF7 binds CUG-motif 3' UTR RNAs and exports them to polysomes via an exportin 1-dependent NES, acting as a cytoplasmic RNA chaperone.\",\n      \"evidence\": \"RNA-IP, CLIP-seq, fractionation, polysome profiling, leptomycin B, NES/RNA-motif mutagenesis\",\n      \"pmids\": [\"34890234\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relationship between RNA-export and TFIID roles not integrated\", \"Structural basis of RNA recognition unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A stabilizing modification was added to the regulatory repertoire: SETD7 methylates TAF7 at K5/K300, causing deubiquitination, stabilization, and increased activity at the cyclin A2 promoter.\",\n      \"evidence\": \"In vitro methylation, K5/K300 mutagenesis, ubiquitination assay, ChIP, reporter assays\",\n      \"pmids\": [\"38904013\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Crosstalk with TRIM26-mediated degradation not tested\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"TAF7 was linked to disease physiology: it directly activates SAA1 transcription to drive TNBC cell invasion and lung metastasis.\",\n      \"evidence\": \"ChIP, knockdown/overexpression, reporter, invasion/migration assays, xenograft metastasis model\",\n      \"pmids\": [\"40083715\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this reflects TFIID or RNA-chaperone activity unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TAF7's distinct activities — TFIID-resident HAT inhibition, CTD-kinase gating, chromatin-mark reading, and cytoplasmic mRNA export — are coordinated within one cell and which signals partition TAF7 between them remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking nuclear transcriptional and cytoplasmic RNA-export functions\", \"Signal-dependent switching between activities uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 2, 3, 15]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [13]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 3, 13]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [3, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2, 6]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 6, 14]}\n    ],\n    \"complexes\": [\"TFIID\"],\n    \"partners\": [\"TAF1\", \"CIITA\", \"MED26\", \"TRIM26\", \"SETD7\", \"VDR\", \"JUN\", \"YY1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}