| 1991 |
TFIID/TBP binds primarily within the minor groove of the TATA box DNA helix, established by replacing thymines and adenines with cytosines and inosines to swap major-groove identity while preserving the minor groove surface. |
Novel base-substitution approach (C/I replacement) combined with DNA-binding assays |
Cell |
High |
1760847
|
| 1992 |
TBP induces DNA bending around the TATA element upon binding, demonstrated with recombinant yeast and human TBP using a permuted binding site/gel retardation assay. |
Permuted binding site/gel retardation assay with recombinant TBP |
Proceedings of the National Academy of Sciences of the United States of America |
High |
1736286
|
| 1992 |
A 12 amino acid region of TBP directly contacts the TATA element and determines DNA-binding specificity; specific substitutions in this region alter specificity from TATAAA to TGTAAA both in yeast and when the equivalent substitutions are introduced into human TBP. |
Genetic selection for altered-specificity mutants, biochemical DNA-binding assays, in vivo transcription assays |
Cell |
High |
1739977
|
| 1992 |
TBP in HeLa extracts exists in two distinct multisubunit complexes (~300 kDa B-TFIID and >700 kDa D-TFIID), both containing the 38 kDa TBP; only the larger complex supports transcriptional activation by acidic or glutamine-rich activators. |
Biochemical fractionation, cofractionation studies, antisera-based detection, in vitro transcription |
Genes & development |
High |
1936986
|
| 1992 |
B-TFIID is composed of two subunits: TBP and a 170 kDa TAF specific to B-TFIID (not present in D-TFIID); purified B-TFIID has (d)ATPase activity. |
Biochemical purification, subunit composition analysis, ATPase activity assay |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
1387711
|
| 1993 |
Recombinant hTAFII250 binds directly to TBP both in vitro and in yeast and participates in the formation of the TFIID complex; the CCG1/hTAFII250 gene is linked to cell-cycle progression. |
Recombinant protein expression, in vitro binding, yeast interaction assays |
Nature |
High |
7680771
|
| 1993 |
p53 binds directly to TBP and cooperates with TBP or partially purified TFIID to enhance binding to a DNA fragment containing both a p53-binding site and a TATA box; p53 strongly inhibits TBP (but not TFIID) binding to a TATA box lacking a p53 site. |
Co-IP, DNA-binding assays (EMSA), in vivo cotransfection transcription assays |
Genes & development |
High |
8405994
|
| 1993 |
p300 co-immunoprecipitates with TBP and shares two additional common phosphoproteins (64 and 59 kDa) with TBP complexes, indicating p300 interacts with TBP (possibly through intermediary proteins). |
Co-immunoprecipitation, partial proteolytic digest comparison |
Oncogene |
Medium |
8502484
|
| 1993 |
Drosophila TAFII60 and human TAFII70 bind weakly to TBP and strongly to TAFII250; in combination with TBP and TAFII250 they form a stable ternary complex; dTAFII60 and hTAFII70 also directly interact with TAFII40. |
Recombinant protein expression, pull-down binding assays |
The EMBO journal |
Medium |
8262073
|
| 1994 |
SL1 TAFIs (TAFI110, 63, 48) can each bind individually and specifically to TBP, and form a stable TBP-TAF complex; binding of SL1 TAFIs to TBP is mutually exclusive with binding of TFIID subunits (TAFII250 or TAFII150), establishing a mechanism for directing TBP into polymerase-selective complexes. |
Reconstituted subunit interaction assays, complementary cDNA expression, biochemical binding competition |
Science |
High |
7801123
|
| 1994 |
Drosophila holo-TFIIA (L/S complex) binds TBP with high affinity and cooperatively with TBP to TATA box DNA (extended DNase footprint); holo-TFIIA stimulates basal transcription and enhances activation by Sp1, VP16, and NTF-1. |
Reconstitution of recombinant TFIIA subunits, subunit interaction studies, DNase footprinting, in vitro transcription |
Genes & development |
High |
7958898
|
| 1994 |
The TBP subunit of TFIID crosslinks specifically to the TATA element; a 150 kDa TAF crosslinks to downstream regions (+10 to +15 and +35 to +47); a >205 kDa TAF crosslinks preferentially to +35 to +42; TAF-DNA interactions downstream are disrupted at elevated salt while TBP-TATA interaction is maintained. |
Protein-DNA crosslinking of TFIID complex |
Nucleic acids research |
Medium |
8139922
|
| 1995 |
Crystal structure of the TFIIB/TBP/TATA-element ternary complex at 2.7 Å resolution: core TFIIB resembles cyclin A and recognizes the preformed TBP-DNA complex through protein-protein and protein-DNA contacts; the TFIIB amino-terminal domain forms the downstream surface where it could fix the transcription start site. |
X-ray crystallography |
Nature |
High |
7675079
|
| 1995 |
Distamycin A and tallimustine bind the DNA minor groove and prevent TBP (and TBP-TFIIA, TBP-TFIIA-TFIIB) binding to the TATA box; once formed, TBP-containing complexes are more resistant to these drugs; both inhibit basal in vitro transcription at similar concentrations. |
EMSA (gel shift), in vitro transcription |
Nucleic acids research |
Medium |
7784168
|
| 1995 |
Electron microscopy of yeast TBP on HIV and adeno promoters shows TBP forms dimers (63 kDa) at the TATA box and higher-order oligomers; TBP dimers bend the DNA approximately 80–90° around the TATA box. |
Electron microscopy (three preparative methods), mass analysis of protein particles |
Journal of molecular biology |
Medium |
7533216
|
| 1997 |
TBP/TFIID binds selectively to cisplatin- or UV-damaged DNA (structural similarity between damaged DNA and TATA box), sequestering TBP away from promoters; microinjection of additional TBP in living human fibroblasts alleviates UV-induced reduction in RNA synthesis. |
Filter binding, in vitro transcription competition, 3D structural analysis, microinjection into living cells |
The EMBO journal |
High |
9405373
|
| 1997 |
TFIIA stabilizes TBP/TATA interactions approximately 10-fold (reduces koff); upstream DNA contacts by TFIIA further stabilize the TFIIA-TBP complex; in the absence of DNA, TFIIA dissociates from TBP rapidly (koff ~4.9×10⁻³ s⁻¹). |
Nitrocellulose filter binding assay (koff measurements), EMSA, nickel-agarose pull-down with His-tagged TFIIA |
Journal of molecular biology |
High |
9300055
|
| 1997 |
TBP-TFIIB interaction is critical for transcription in vitro; an altered-specificity TATA-TBP-TFIIB array showed that many activators use the known TBP-TFIIB interaction to stimulate transcription in human cells, but a glutamine-rich Sp1 activation domain activates independently of this interaction. |
Rationally designed altered-specificity TBP-TFIIB interaction, in vivo transcription assays in human cells |
Science |
High |
9012349
|
| 1998 |
TAFIIs (specifically TAFII250) inhibit TBP-DNA binding and TBP-TFIIA binding; TFIIA overcomes TAFII-mediated inhibition of TBP-DNA binding by competing with TAFII250 for access to TBP; limited proteolysis of TFIID relieves inhibition of TBP-DNA binding. |
EMSA, DNase I footprinting, in vitro transcription, temperature-sensitive cell line (ts13) |
The Journal of biological chemistry |
High |
9603936
|
| 1999 |
TFIIA promotes dissociation of TBP dimers (which block DNA binding) and accelerates TBP binding kinetics; TFIID dimer dissociation is slow and rate-limiting in DNA binding, and TFIIA induces rapid dissociation of TFIID dimers to facilitate promoter loading. |
Biochemical dimerization assays, kinetic DNA-binding assays |
Molecular cell |
High |
10518227
|
| 1999 |
TBP binding in vivo is regulated: Mot1 prevents TBP binding to inactive promoters, and activator-mediated stimulation of TBP binding requires TFIIB and Srb4; TBP binding generally correlates with transcriptional activity across endogenous yeast genes. |
DNA-crosslinking/immunoprecipitation (in vivo), mutant yeast strains (genetic epistasis) |
Nature |
High |
10376604
|
| 1999 |
TBP-related factor TRF2 (TBPL1) binds TFIIA and TFIIB but does not bind canonical TATA boxes; TRF2 is associated with distinct chromosomal loci from TBP in Drosophila, suggesting different promoter specificity. |
Protein interaction assays, Drosophila polytene chromosome staining |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
10220372
|
| 2000 |
In vivo, TBP exists in at least two transcriptionally active forms: a TAF-containing form (TFIID) and a TAF-independent form; promoter occupancy by TAFs does not universally correlate with transcriptional activity, unlike TBP, TFIIA, and TFIIB occupancy. |
Chromatin immunoprecipitation (ChIP) at yeast promoters, genome-wide expression analysis |
Science |
High |
10818000
|
| 2000 |
TBP-related factor TRF1 preferentially binds and directs transcription from the tudor gene promoter in Drosophila, a TRF1-responsive promoter distinct from TBP-regulated promoters. |
Polytene chromosome staining, ChIP, mRNA analysis, cotransfection assays, in vitro transcription reconstitution, DNase I footprinting |
Science |
High |
10797011
|
| 2001 |
MOT1 uses ATP hydrolysis to remove TBP from DNA; MOT1 requires a 17 bp double-stranded DNA 'handle' upstream of the TATA box; TBP-DNA disruption does not require DNA strand separation, bending, or helix twisting, suggesting translocation along the handle drives disruption. |
In vitro ATPase/disruption assays with template variants, mutant DNA substrates |
The EMBO journal |
High |
11296235
|
| 2002 |
GFP-TBP stably associates with condensed mitotic chromosomes (no FRAP signal during mitosis); in interphase cells, GFP-TBP shows ~100-fold slower FRAP than TFIIB; endogenous TBP and TAFs cofractionate with mitotic chromatin, suggesting TBP-TAF complexes remain promoter-bound for multiple rounds of transcription. |
FRAP of GFP-TBP in live HeLa cells, chromatin fractionation |
Molecular biology of the cell |
High |
11809839
|
| 2003 |
p53 represses RNA polymerase III transcription through direct interaction with TBP; overexpressing TBP reverses p53-mediated inhibition of tRNA gene transcription; p53 does not disrupt TBP-Brf1 interaction but prevents Brf1 complexes from associating with TFIIIC2 and RNA pol III; ChIP shows TFIIIB occupancy decreases upon p53 induction. |
In vitro transcription, overexpression rescue, chromatin immunoprecipitation (ChIP), co-immunoprecipitation |
The EMBO journal |
High |
12773395
|
| 2004 |
RNA aptamers generated against yeast TBP bind TBP competitively with TATA-DNA and some actively disrupt preformed TBP-TATA complexes even in the context of TFIIB and TFIIA; aptamers inhibit transcription in crude extracts, revealing dynamic TBP interactions during initiation and reinitiation. |
SELEX, aptamer binding assays, in vitro transcription with crude extracts |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
15103022
|
| 2004 |
Immunomapping of yeast TFIID by EM revealed TBP is located in the linker domain between lobes A and C of the trilobed TFIID structure, with the N-terminal 100 residues of TAF1 spanning over TBP. |
Electron microscopy, immunomapping with antibodies against TFIID subunits |
The EMBO journal |
Medium |
14765106
|
| 2006 |
SAGA binds TBP directly via its Spt8 subunit (and Ada1); Spt8 and SAGA compete with DNA (rather than forming a triple complex) to bind TBP, supporting a handoff model where SAGA transfers TBP to the TATA box rather than binding together with TBP at the promoter. |
Chemical crosslinking to identify SAGA-TBP contacts, direct binding assays (competition with DNA and TBP dimer) |
The EMBO journal |
High |
16888622
|
| 2006 |
The Med8 N-terminal domain of the Mediator head subcomplex Med8-Med18-Med20 binds TBP in vitro and is essential in vivo; the Med8/18/20 subcomplex contains a putative multipartite TBP-binding site in the Mediator head. |
X-ray crystallography of Med8C/18/20 submodule, in vitro TBP-binding assays, genetic complementation |
Nature structural & molecular biology |
High |
16964259
|
| 2006 |
Brd2 is a TBP-associated protein; a 26 amino acid peptide in the first bromodomain of Brd2 mediates Brd2-TBP interaction; serum stimulation induces formation of a Brd2-E2F-1-TBP complex in vivo, with Brd2 recruiting TBP into the E2F-1 transcriptional complex. |
Co-immunoprecipitation, domain mapping, overexpression assays, luciferase reporter assays |
Molecular and cellular biochemistry |
Medium |
17111193
|
| 2008 |
During mitosis, TBP recruits PP2A to active gene promoters; the TBP-PP2A complex dephosphorylates and inactivates condensin at these promoters to prevent chromatin compaction, thereby bookmarking previously active genes for re-activation in daughter cells. |
Co-immunoprecipitation, ChIP-on-chip, functional assays for condensin inactivation |
Nature cell biology |
High |
18931662
|
| 2010 |
TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation; cryo-EM structures reveal Rap1 and TFIIA bind TFIID simultaneously, TFIIA undergoes a Rap1-induced conformational change that increases exposure of TBP within TFIID; a large DNA loop forms between the activator site and proximal promoter, locked by a TFIIA-Rap1 protein bridge. |
Cryo-electron microscopy, structural reconstruction of TFIID-TFIIA-Rap1-DNA complexes |
Nature |
High |
20559389
|
| 2013 |
Human TFIID exists in two predominant structural states differing by ~100 Å translocation of lobe A; TFIIA and promoter DNA together facilitate transition to a rearranged state that enables promoter recognition; TATA, Inr, MTE, and DPE promoter motifs were mapped within the TFIID-TFIIA-DNA structure. |
Single-particle electron microscopy (cryo-EM), DNA labeling, DNase footprinting |
Cell |
High |
23332750
|
| 2014 |
TRF2 (TBPL1/TRF2), not TBP, is required for transcription of TCT-dependent ribosomal protein genes in Drosophila and humans; TBP depletion does not affect TCT-dependent transcription, while TRF2 depletion does; purified TRF2 activates TCT but not TATA promoters in vitro. |
Overexpression and depletion of TBP/TRF2, in vitro transcription with purified TRF2, ChIP-seq |
Genes & development |
High |
24958592
|
| 2014 |
Age-related decline in Hsc70 chaperone activity leads to increased mutant TBP accumulation in SCA17 mice; mutant TBP shows decreased association with XBP1s, resulting in reduced transcription of MANF; expression of Hsc70 improves TBP-XBP1s interaction and MANF transcription. |
Inducible knock-in mouse model, co-immunoprecipitation, gene expression analysis, MANF overexpression rescue |
Neuron |
Medium |
24462098
|
| 2015 |
TBP interacts with the Cnd2 kleisin subunit of condensin and recruits condensin onto RNA polymerase III-transcribed genes and highly transcribed Pol II genes in fission yeast; disruption of the Cnd2-TBP interaction causes defects in condensin localization, mitotic chromosome assembly, chromosome segregation, and cellular lethality. |
Co-immunoprecipitation, ChIP, genetic analysis with interaction-disrupting mutants |
Molecular cell |
High |
26257282
|
| 2015 |
TBP protein levels are regulated by the ubiquitin-proteasome system; E3 ligase Huwe1 targets TBP for K48-linked ubiquitination and proteasomal degradation; deubiquitinase USP10 antagonizes Huwe1 and protects TBP from degradation; upregulation of Huwe1 during myogenesis induces TBP degradation and drives myotube differentiation. |
In vitro ubiquitination assay with biochemical fractionation, mass spectrometry identification of Huwe1, cell-based functional assays |
eLife |
High |
26393420
|
| 2016 |
Cryo-EM structure of human TFIID with TFIIA and core promoter DNA at sub-nanometre resolution shows TAF1 and TAF2 mediate major interactions with the downstream promoter; TFIIA bridges the TBP-TATA complex with lobe B of TFIID; all core promoter elements are contacted by TFIID subunits. |
Single-particle cryo-electron microscopy, structural analysis |
Nature |
High |
27007846
|
| 2017 |
TAF11 and TAF13 form a ternary complex with TBP via the TAF11/TAF13 histone-fold domains; TAF11/TAF13 competes with TATA-box DNA and with the TAF1 N-terminal domain (TAND1) for TBP binding; the highly conserved C-terminal TBP-interaction domain (CTID) of TAF13 is essential for cell growth; TAF11/TAF13 interacts with the DNA-binding surface of TBP. |
Crystal structure of TAF11/TAF13/TBP complex (2.4 Å), cross-linking mass spectrometry, biochemical competition assays, genetic complementation |
eLife |
High |
29111974
|
| 2018 |
Cryo-EM of human TFIID with TFIIA and promoter DNA reveals five structural states; initial TFIID binding to the downstream promoter positions upstream DNA and facilitates scanning of TBP for a TATA box, followed by engagement of the promoter — defining a mechanism for TBP loading onto promoter DNA by TFIID. |
Cryo-electron microscopy, chemical cross-linking mass spectrometry, biochemical reconstitution |
Science |
High |
30442764
|
| 2018 |
TBP remains stably bound to active gene promoters on mitotic chromosomes in mouse ES cells (average residence time of minutes vs. seconds for typical TFs, by single-molecule live imaging); acute TBP degradation reduces RNA Pol II association with mitotic chromosomes and impairs transcriptional reactivation after mitosis. |
Live-cell single-molecule imaging, drug-inducible degron system, ChIP |
eLife |
High |
29939130
|
| 2018 |
Chaperonin CCT specifically associates with nascent TAF5 and hands it off to TAF6-TAF9, acting as a checkpoint for TFIID assembly; TAF5-TAF6-TAF9 form a cytoplasmic submodule with novel interactions essential for TFIID integrity; TAF9 allocation between TFIID and SAGA is regulated by these submodule interactions. |
Quantitative proteomics, structural analysis, mutational analysis, mass spectrometry of submodules |
Nature structural & molecular biology |
High |
30510221
|
| 2019 |
H3K4me3Q5ser (combinatorial serotonylation and methylation on histone H3) potentiates TFIID binding to H3K4me3 nucleosomes; tissue transglutaminase 2 serotonylates H3 at Q5 on H3K4me3-marked nucleosomes; ectopic expression of a H3 mutant that cannot be serotonylated alters H3K4me3Q5ser-target gene expression and impairs differentiation. |
In vitro enzyme assay (transglutaminase), genome-wide chromatin analysis, TFIID binding assay, H3 mutant cell lines |
Nature |
High |
30867594
|
| 2019 |
Two discrete regions of MYC (amino acids 98–111 and 115–124) interact with TBP; a crystal structure (2.4 Å) shows MYC aa 98–111 interacts with TBP in the presence of TAF1 TAND1; MYC aa 115–124 resembles a TBP anchor motif; MYC mutants that abrogate TBP interaction compromise MYC transcriptional activity. |
2.4 Å crystal structure, biochemical binding assays, site-specific MYC mutagenesis with functional assays |
Nature structural & molecular biology |
High |
31686052
|
| 2020 |
Cryo-EM structure of yeast SAGA with bound TBP reveals an octamer of histone-fold domains in the SAGA core that forms a peripheral site for TBP where steric hindrance represses spurious DNA binding; biochemical analysis shows TBP delivery from SAGA to promoter DNA requires TFIIA and correlates with TBP-DNA affinity, supporting a handoff mechanism. |
Cryo-electron microscopy (3.5 Å core resolution), biochemical TBP delivery assays |
Nature |
High |
31969704
|
| 2020 |
TFIID is required for RNA Polymerase II promoter-proximal pausing; replacement of TFIID with TBP alone in a purified reconstituted in vitro transcription system abolishes pausing; acute depletion of TFIID subunits in human and Drosophila cells disrupts genome-wide RNAPII pausing. |
Reconstituted in vitro transcription with purified factors, drug-inducible TFIID subunit depletion, PRO-seq |
Molecular cell |
High |
32229306
|
| 2021 |
TBP can bind to a nucleosome containing the Widom-601 sequence; TFIIA stabilizes TBP-nucleosome binding; cryo-EM structures show TBP binds at SHL -6 (TATA-like, TFIIA-independent) and SHL +2 (GC-rich, TFIIA-dependent, with detachment of upstream terminal DNA from histone octamer); TBP-nucleosome complexes are sterically incompatible with PIC assembly. |
Cryo-electron microscopy (three structures), biochemical binding assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
34301908
|
| 2022 |
TIF1γ binds TBP in competition with TAF15, displacing TAF15 from the TAF15/TBP complex; TIF1γ also multi-mono-ubiquitylates TAF15 and drives its nuclear export; the TAF15/TBP complex is required for IL-6 transactivation-induced EMT in lung adenocarcinoma cells. |
Co-immunoprecipitation, competition binding assays, ubiquitylation assays, nuclear export assays, cell functional assays |
Cell reports |
Medium |
36261009
|
| 2023 |
Human TFIID biogenesis occurs co-translationally; all protein heterodimerization steps occur during protein synthesis; TAF1 acts as a flexible scaffold that drives co-translational recruitment of TFIID submodules preassembled in the cytoplasm onto the nascent TAF1 polypeptide. |
RNA-immunoprecipitation (RIP), single-molecule imaging, proteomics, structure-function analyses |
Nature structural & molecular biology |
High |
37386215
|
| 2015 |
Large polyQ repeats (105Q) in TBP preferentially cause muscle degeneration and reduce expression of muscle-specific genes by decreasing the association of MyoD with TBP and with DNA promoters; smaller polyQ repeats do not show this effect, demonstrating polyQ length-dependent differential protein interactions. |
Knockin mouse models, co-immunoprecipitation, ChIP, direct muscle expression of TBP with different polyQ lengths |
Cell reports |
Medium |
26387956
|