Affinage

TAF6

Transcription initiation factor TFIID subunit 6 · UniProt P49848

Length
677 aa
Mass
72.7 kDa
Annotated
2026-06-10
15 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAF6 (TAFII70/TAFII80) is a core architectural subunit of the general transcription machinery that organizes protein-protein contacts within TFIID and SAGA and bridges these complexes to regulatory factors (PMID:7667268, PMID:29485702). Within TFIID it nucleates assembly through a histone-fold domain that drives heterodimerization with TAF9 (TAFII22) in a histone octamer-like arrangement, while a C-terminal domain comprising five conserved HEAT repeats provides a structurally distinct interaction surface that also contributes to TAF9 binding and is modulated by TAF5 (PMID:9133630, PMID:22696218). The histone fold and HEAT domains have non-equivalent roles in complex assembly: in yeast the HFD supports TAF6-TAF9 heterodimerization while the HEAT domain is specifically required for SAGA association and resistance to elongation inhibitors, with both domains needed for TFIID and SAGA promoter occupancy; in human SAGA the TAF6L HEAT surface docks the splicing-factor module [PMID:29485702, PMID:bio_10.1101_2025.07.31.667873]. TAF6 establishes a defined network of contacts through three mapped interaction domains, binding TAF1 (TAFII250), TAF4 (TAFII31), TAF11 (TAFII20), and TBP among TFIID subunits and the general factors TFIIE alpha and TFIIF alpha (RAP74) (PMID:7667268, PMID:9133630). It also serves as a platform for transcriptional control: the corepressor N-CoR binds TAF6 and locks the initiation machinery in an inactive state by ablating the TFIIB-TAF6/TAF11 interactions required for initiation (PMID:9611234). TAF6 supports cell cycle progression and tumor-relevant transcription, acting downstream of the non-catalytic function of SETD1A in an E2F4-regulated axis to drive G1/S progression (PMID:40846851), exhibiting isoform-specific growth suppression through interaction with GADD45a (PMID:15328371), and physically interacting with p53 to support its transcriptional output (PMID:41868912).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1993 Medium

    Established TAF6 as a stable TFIID subunit by showing it binds TBP and TAFII250 to form a ternary complex, defining its role in scaffolding the core TFIID architecture.

    Evidence Recombinant protein expression and coimmunoprecipitation/ternary complex assays, including conservation with Drosophila TAFII60

    PMID:8262073

    Open questions at the time
    • Did not map the interaction surfaces
    • Functional consequence for transcription not tested
  2. 1995 High

    Resolved how TAF6 integrates into the transcription machinery by mapping three distinct interaction domains for TFIID subunits, TBP, and general transcription factors, defining it as a multi-contact hub.

    Evidence Reciprocal Co-IP with recombinant/expressed proteins plus deletion and mutation mapping

    PMID:7667268

    Open questions at the time
    • Structural basis of the contacts not resolved
    • Functional requirement of each contact for transcription untested
  3. 1997 Medium

    Showed the histone fold motif drives TAF6 heterodimerization with TAF9/TAFII22, supporting a histone octamer-like sub-assembly inside TFIID.

    Evidence Yeast two-hybrid with histone-fold-targeted deletion/mutation constructs

    PMID:9133630

    Open questions at the time
    • Single method (Y2H)
    • Did not address contributions of regions outside the histone fold
  4. 1998 Medium

    Linked TAF6 to active transcriptional repression by showing the corepressor N-CoR binds TAF6 and disrupts the TFIIB-TAF interactions needed for initiation.

    Evidence In vitro binding, in vivo Co-IP, and functional transcription assays

    PMID:9611234

    Open questions at the time
    • N-CoR binding site on TAF6 not mapped
    • Promoter context and physiological targets unaddressed
  5. 2001 Medium

    Identified Cajal bodies as a subnuclear site where TAF6 accumulates, implicating these structures in assembly of the transcription machinery.

    Evidence Antibody immunostaining and microinjection/expression of tagged TAF6 in newt oocyte germinal vesicles

    PMID:11768213

    Open questions at the time
    • Functional role of Cajal-body localization not established
    • Observed in oocytes; somatic relevance unclear
  6. 2004 Medium

    Revealed isoform-specific function by showing the TAFII70 isoform, but not TAFII80, induces G2 arrest and growth suppression through a required GADD45a interaction independent of p53.

    Evidence Isoform overexpression, cell cycle analysis, Co-IP, and epistasis in GADD45a-null cells

    PMID:15328371

    Open questions at the time
    • Mechanism connecting TAF6 isoform to GADD45a-dependent arrest unknown
    • Endogenous isoform balance not quantified
  7. 2012 High

    Defined the C-terminal HEAT repeat domain at atomic resolution and demonstrated it contributes to TAF9 binding beyond the histone fold, with TAF5 modulating the interaction.

    Evidence 1.9 A crystal structure (A. locustae TAF6C), site-directed mutagenesis of human TAF6, Co-IP, and ternary pulldowns

    PMID:22696218

    Open questions at the time
    • Structure from an insect/microsporidian ortholog, not full-length human TFIID
    • Functional consequence of HEAT-mediated TAF9 binding in vivo untested here
  8. 2018 High

    Dissected the division of labor between TAF6 domains, showing the HFD drives TAF9 heterodimerization while the HEAT domain is selectively required for SAGA association and that both are needed for TFIID/SAGA promoter occupancy.

    Evidence Yeast ts mutants, Co-IP, ChIP, in vitro heterodimerization, and genetic suppressor analysis

    PMID:29485702

    Open questions at the time
    • Performed in yeast; human SAGA-specific assignment not directly shown here
    • Molecular basis of HEAT-domain SAGA selectivity not resolved
  9. 2025 Medium

    Placed TAF6 in a SETD1A-dependent proliferation axis, showing TAF6 expression requires the non-catalytic FLOS domain of SETD1A and that TAF6 is needed for G1/S progression, with E2F4 acting upstream.

    Evidence Pooled CRISPR screen, cDNA rescue, knockdown, and cell cycle analysis in gastric cancer cells

    PMID:40846851

    Open questions at the time
    • Direct transcriptional targets driving G1/S not identified
    • Mechanism by which SETD1A controls TAF6 expression unresolved
  10. 2025 Medium

    Showed structurally how the TAF6 HEAT surface specializes complex assembly, with the SAGA-specific paralog TAF6L HEAT domain providing the docking site for the splicing-factor module.

    Evidence Cryo-EM of endogenous human SAGA (preprint)

    PMID:bio_10.1101_2025.07.31.667873

    Open questions at the time
    • Preprint, not peer-reviewed
    • Applies to the TAF6L paralog rather than canonical TFIID TAF6
  11. 2026 Medium

    Connected TAF6 to p53-dependent transcription, showing a direct TAF6-p53 interaction that lncRNA ZBTB46-AS1 competitively disrupts to suppress p21 induction.

    Evidence RNA pull-down, RIP, Co-IP, and dual-luciferase reporter assays in ovarian cancer cells

    PMID:41868912

    Open questions at the time
    • TAF6 region mediating p53 binding not mapped
    • Generality beyond ovarian cancer context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAF6's two domains are differentially deployed to specify TFIID versus SAGA assembly in human cells, and how its contacts with regulators (N-CoR, p53, GADD45a) reshape initiation at specific promoters, remain mechanistically open.
  • No integrated structural model of human TFIID showing TAF6 regulatory contacts
  • Endogenous gene targets of TAF6-dependent regulation not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2
Partners
GADD45ANCOR1TAF1TAF9TBPTFIIE ALPHATFIIF ALPHATP53
Complex memberships
SAGATFIID

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Human TAFII70 (TAF6) binds weakly to TBP and tightly to TAFII250; together with TBP and TAFII250 forms a stable ternary complex; also directly interacts with dTAFII40 (TAF9 ortholog). Interactions are conserved between Drosophila TAFII60 and human TAFII70. Recombinant protein expression, coimmunoprecipitation, ternary complex formation assays The EMBO journal Medium 8262073
1995 Human TAFII80 (TAF6) interacts with TAFII250, TAFII31, TAFII20, and TBP, but not TAFII55; also interacts with TFIIE alpha and TFIIF alpha (RAP74) but not TFIIB, TFIIE beta, or TFIIF beta (RAP30). Mutational analysis defined three distinct interaction domains: N-terminus (residues 1–100) for TAFII31 and TAFII20, C-terminal region (residues 203–276) for TAFII250 and TFIIF alpha, and C-terminal region (residues 377–505) for TBP and TFIIE alpha. Coimmunoprecipitation with recombinant and expressed proteins; deletion/mutation mapping Proceedings of the National Academy of Sciences of the United States of America High 7667268
1997 The histone fold motifs of human TAFII80 (TAF6) and TAFII22 are indispensable for their mutual interaction, supporting a histone octamer-like partial TAF complex within TFIID. Yeast two-hybrid system with deletion/mutation constructs targeting histone fold motifs Journal of biochemistry Medium 9133630
1998 N-CoR (and splice variants RIP13a and RIP13Delta1) directly interacts with TAFII70 (TAF6) in vitro. N-CoR can simultaneously interact with TFIIB, TAFII32, and TAFII70 in a non-competitive manner, and N-CoR expression ablates the functional interaction between TFIIB and TAFII32 required for transcription initiation. In vitro binding assays, co-immunoprecipitation in vivo, functional transcription assays Nucleic acids research Medium 9611234
2001 TAFII70 (TAF6) protein localizes to Cajal bodies in the germinal vesicle (nucleus) of newt oocytes, associating with both chromosome-attached and free Cajal bodies, supporting a role for Cajal bodies as assembly sites for the transcription machinery. Immunostaining with anti-hTAFII70 monoclonal antibody; microinjection of myc-tagged PwTAFII70 transcripts into oocyte cytoplasm followed by detection in Cajal bodies Genome Medium 11768213
2004 The TAFII70 isoform (but not TAFII80 isoform) of TAF6 causes G2 arrest and growth suppression of breast epithelial cells in a p53-independent manner, and uniquely forms a protein-protein interaction with GADD45a; GADD45a-null cells are resistant to TAFII70-mediated growth inhibition, establishing GADD45a as functionally required downstream. Isoform overexpression in cell lines, cell cycle analysis, co-immunoprecipitation of TAFII70-GADD45a interaction, GADD45a null cell epistasis experiment Molecular cancer research : MCR Medium 15328371
2012 The C-terminal domain of TAF6 contains five conserved HEAT repeats (crystal structure at 1.9 Å from Antonospora locustae TAF6C). Mutations in the HEAT repeat domain impair TAF6-TAF9 interaction beyond just the histone fold motifs; TAF5 modulates the TAF6-TAF9 interaction, further weakening it in a TAF5-TAF6-TAF9 ternary context. X-ray crystallography (1.9 Å); site-directed mutagenesis in full-length human TAF6; co-immunoprecipitation in HeLa cells; ternary complex pulldown assays The Journal of biological chemistry High 22696218
2018 In yeast, TAF6's histone-fold domain (HFD) is required for TAF6-TAF9 heterodimerization in vitro but is dispensable for TFIID/SAGA association in cell extracts; the HEAT repeat domain is required for TAF6's interaction with SAGA (but not TFIID) and for resistance to transcription elongation inhibitors; both HFD and HEAT domain mutations abolish TFIID and SAGA promoter occupancy. Genetic suppression: HEAT domain mutant temperature-sensitivity is suppressed by overexpression of TAF9, TAF12, or TBP; HFD mutant is suppressed by TAF5 but not TAF9, TAF12, or TBP. Yeast genetics (ts mutants), co-immunoprecipitation, ChIP assays, recombinant protein heterodimerization, genetic suppressor analysis The FEBS journal High 29485702
2025 Non-catalytic FLOS domain of SETD1A is essential for TAF6 expression in gastric cancer cells; TAF6 acts downstream of SETD1A's non-catalytic function (established by CRISPR screen and cDNA rescue), and both SETD1A and TAF6 are required for G1/S cell cycle progression. E2F4 supports TAF6 expression upstream of SETD1A. Pooled CRISPR screen, cDNA rescue experiment, cell cycle analysis, expression knockdown Cell death & disease Medium 40846851
2025 In human SAGA, the TAF6L HEAT repeat domain provides a docking surface for the splicing-factor module (SPL); structural differences between TAF6L (SAGA-specific) and canonical TAF6 (TFIID) are directly implicated in structural rearrangements required to accommodate SPL into SAGA. Cryo-EM structure of endogenous human SAGA purified by affinity-ligand without CRISPR engineering bioRxivpreprint Medium bio_10.1101_2025.07.31.667873
2026 TAF6 physically interacts with p53 (established by co-immunoprecipitation); lncRNA ZBTB46-AS1 competes with p53 for TAF6 binding, attenuating TAF6-p53 interaction and suppressing p53 transcriptional activity and p21 expression in ovarian cancer cells. RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation, dual-luciferase reporter assay American journal of translational research Medium 41868912

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The corepressor N-CoR and its variants RIP13a and RIP13Delta1 directly interact with the basal transcription factors TFIIB, TAFII32 and TAFII70. Nucleic acids research 114 9611234
1995 Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors. Proceedings of the National Academy of Sciences of the United States of America 75 7667268
1993 Cloning and expression of Drosophila TAFII60 and human TAFII70 reveal conserved interactions with other subunits of TFIID. The EMBO journal 71 8262073
2012 TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein. The Journal of biological chemistry 24 22696218
1997 The involvement of the histone fold motifs in the mutual interaction between human TAF(II)80 and TAF(II)22. Journal of biochemistry 13 9133630
2004 TAFII70 isoform-specific growth suppression correlates with its ability to complex with the GADD45a protein. Molecular cancer research : MCR 11 15328371
2020 Proteomics and molecular network analyses reveal that the interaction between the TAT-DCF1 peptide and TAF6 induces an antitumor effect in glioma cells. Molecular omics 5 31899468
2014 Alternative splicing of TAF6: downstream transcriptome impacts and upstream RNA splice control elements. PloS one 5 25025302
2001 TAFII70 protein in Cajal bodies of the amphibian germinal vesicle. Genome 4 11768213
2022 Novel compound heterozygous variants in the TAF6 gene in a patient with Alazami-Yuan syndrome: A case report. World journal of clinical cases 3 35317131
2018 Mutational analysis of TAF6 revealed the essential requirement of the histone-fold domain and the HEAT repeat domain for transcriptional activation. The FEBS journal 3 29485702
2025 Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle. Cell death & disease 2 40846851
2024 Taenia solium TAF6 and TAF9 bind to a downstream promoter element present in the Tstbp1 gene core promoter. PloS one 2 39208271
2000 Expression of TAFII70 RNA and protein during oogenesis and development of the amphibian Pleurodeles waltl. Mechanisms of development 1 11091092
2026 Long non-coding RNA ZBTB46-AS1 promotes ovarian cancer progression through regulation of p53 activity by TAF6 protein. American journal of translational research 0 41868912

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