Affinage

Showing GTF2B — TFIIB is a alias.

GTF2B

Transcription initiation factor IIB · UniProt Q00403

Length
316 aa
Mass
34.8 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GTF2B encodes TFIIB, an essential general transcription factor for RNA polymerase II that nucleates preinitiation complex assembly and governs the transition from promoter recognition to productive initiation (PMID:1946368, PMID:35947745). TFIIB is organized into two functionally separable modules: a C-terminal core of two cyclin A–like direct repeats that recognizes the preformed TBP–TATA complex and extends contacts to promoter DNA, and an N-terminal zinc-ribbon region that recruits RNA polymerase II–TFIIF; mutation of the core abolishes Pol II recruitment without disrupting TBP binding, while the zinc ribbon is dispensable for TBP contact (PMID:8516312, PMID:8516311, PMID:8413225, PMID:7675079, PMID:7671313). Within the assembled complex, TFIIB sits beneath the concave face of TBP and surrounds promoter DNA, and its zinc ribbon contacts the Pol II Dock domain near the RNA exit path while its linker, reader, and core elements reach over the active-center cleft to position template DNA, assist DNA opening, and scan for the transcription start site (PMID:7637813, PMID:8855228, PMID:14536083, PMID:14963322, PMID:19820686, PMID:23151482). Accordingly, TFIIB and TATA-box mutations impair transcription after recruitment, and TFIIB determines start-site selection through genetic and functional interactions with the Pol II Rpb1, Rpb2, and Rpb9 subunits and with TFIIF (PMID:1547497, PMID:8264591, PMID:7724527, PMID:8692696, PMID:9651390, PMID:9887099, PMID:15082791). As RNA synthesis proceeds beyond ~12–13 nt the growing transcript and upstream DNA rewinding sterically displace the B-reader and B-linker, triggering TFIIB release and promoter clearance, with TFIIF stabilizing TFIIB in early elongation until that point (PMID:15989968, PMID:19820686, PMID:21896726, PMID:23151482). TFIIB additionally recognizes flanking core-promoter BRE elements through distinct DNA-binding modules, links initiation to 3′ processing via serine-65 phosphorylation that controls CstF/CPSF recruitment, and participates in Ssu72-dependent gene looping by associating with both promoters and terminators (PMID:11711430, PMID:16230532, PMID:17803944, PMID:20226668, PMID:35947745). TFIIB is also a direct convergence point for transcriptional regulators, contacting the acidic activator VP16 and nuclear hormone receptors among others to enhance its recruitment or induce productive conformational changes (PMID:1922364, PMID:1517211, PMID:8415616, PMID:7878015, PMID:9609687, PMID:10077585). Single-molecule imaging shows TFIIB promoter binding is highly transient and is stabilized only upon Pol II–TFIIF recruitment, defining a kinetic checkpoint in PIC progression (PMID:27798851).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1991 High

    Established TFIIB as a discrete, essential basal factor required for Pol II transcription initiation, defining the molecular entity itself.

    Evidence protein purification to homogeneity, cDNA cloning, and in vitro transcription reconstitution

    PMID:1946368

    Open questions at the time
    • No structural model of how TFIIB engages the initiation machinery
    • Molecular basis of essentiality not defined
  2. 1991 High

    Showed that an acidic activator directly contacts TFIIB to accelerate a rate-limiting recruitment step, establishing TFIIB as a target of transcriptional activation.

    Evidence affinity chromatography with recombinant VP16 and TFIIB plus in vitro transcription rate measurement

    PMID:1922364

    Open questions at the time
    • Surface on TFIIB contacted by VP16 not mapped
    • Whether all activators use this route unknown
  3. 1992 High

    Demonstrated in vivo that TFIIB is a determinant of transcription start-site selection, extending its role beyond simple assembly.

    Evidence yeast SUA7 suppressor genetics and primer-extension start-site mapping at cyc1 and ADH1

    PMID:1547497

    Open questions at the time
    • Mechanism by which TFIIB sets the start site not resolved
    • Pol II partners in selection not yet identified
  4. 1993 High

    Resolved TFIIB into separable N-terminal (Pol II recruitment) and C-terminal (TBP binding) functional domains, defining its bridging architecture.

    Evidence site-directed and deletion mutagenesis, limited proteolysis, footprinting, and in vitro transcription/TBP-binding assays

    PMID:8413225 PMID:8516311 PMID:8516312

    Open questions at the time
    • Atomic structure of the domains not yet known
    • How the two domains coordinate during assembly unclear
  5. 1992 Medium

    Identified nuclear hormone receptors as direct TFIIB-binding regulators, showing receptor transactivation and hormone-modulated silencing operate through TFIIB.

    Evidence recombinant binding/GST pulldown and reporter cotransfection for COUP-TF, ER, PR, thyroid and vitamin D receptors

    PMID:1517211 PMID:7623841 PMID:7878015 PMID:8415616

    Open questions at the time
    • Binding surfaces partially mapped
    • Functional consequence for PIC kinetics not quantified in all cases
  6. 1994 High

    Showed TFIIB can support minimal initiation and that its start-site function is tied to specific Pol II subunits, placing it in a defined functional network with the polymerase.

    Evidence reconstituted YY1/TFIIB/Pol II transcription and sua7–sua8(RPB1) synthetic lethality with start-site mapping

    PMID:8137426 PMID:8264591

    Open questions at the time
    • Physical basis of the TFIIB–Rpb1 interaction not defined
    • TBP-independent route physiological relevance unclear
  7. 1995 High

    Provided the structural basis for TFIIB recognition of the TBP–TATA complex, revealing a cyclin A–like fold and DNA contacts flanking the TATA box.

    Evidence 2.7 Å crystal structure of TFIIB–TBP–TATA, solution NMR of the core domain, and hydroxyl-radical footprinting

    PMID:7637813 PMID:7671313 PMID:7675079

    Open questions at the time
    • Pol II-bound conformation not captured
    • Position of the N-terminal zinc ribbon relative to Pol II unresolved
  8. 1996 High

    Mapped TFIIB as part of a DNA-encircling clamp and defined its genetic partners in TFIIF, refining the geometry and network of the early complex.

    Evidence site-specific protein–DNA photocrosslinking of the TBP–TFIIA–TFIIB–DNA complex and SSU71/TFG1 suppressor genetics

    PMID:7724527 PMID:8855228

    Open questions at the time
    • Direct TFIIB–TFIIF contact surface not yet defined
    • Order of clamp assembly steps unclear
  9. 1998 High

    Distinguished post-recruitment functions of TFIIB and separated its zinc-ribbon (Pol II binding) from an adjacent start-site-selection homology block.

    Evidence immobilized-template PIC assays with E62G mutant and mutagenesis dissecting yeast TFIIB N-terminal domains

    PMID:9651390 PMID:9887099

    Open questions at the time
    • Structural correlate of the start-site homology block lacking
    • Catalytic contribution to initiation not yet visualized
  10. 2001 High

    Defined TFIIB recognition of core-promoter BRE elements and showed activators can modulate this DNA recognition, linking TFIIB to promoter-strength control.

    Evidence transcription assays with BRE-mutant promoters and protein–DNA footprinting

    PMID:11711430

    Open questions at the time
    • Downstream BRE recognition module not yet identified
    • Generality across promoter classes untested
  11. 2004 High

    Delivered the Pol II–TFIIB structure showing the zinc ribbon at the Dock domain and the B-finger reaching into the active center, plus a second BRE-binding module, unifying the assembly and initiation roles.

    Evidence X-ray crystallography of Pol II–TFIIB, crosslinking/hydroxyl-radical probing, B-finger/Rpb2 genetics, and downstream-BRE DNA-binding assays

    PMID:14536083 PMID:14963322 PMID:15082791 PMID:16230532

    Open questions at the time
    • Resolution insufficient to model template-strand path fully
    • How the B-finger times initiation not resolved
  12. 2005 High

    Linked B-finger displacement to transcription-bubble collapse and promoter clearance, establishing TFIIB's role in the initiation-to-elongation transition.

    Evidence permanganate footprinting of bubbles across promoter-spacing mutants with quantitative elongation assays

    PMID:15989968

    Open questions at the time
    • Exact RNA length triggering displacement defined only functionally here
    • Coupling to TFIIH release mechanistically incomplete
  13. 2007 High

    Revealed a transcription-architectural role for TFIIB in Ssu72-dependent gene looping by bridging promoters and terminators.

    Evidence ChIP and 3C across multiple loci with the looping-defective E62K mutant

    PMID:17803944

    Open questions at the time
    • Direct TFIIB–terminator contacts not biochemically reconstituted
    • Functional output of looping for re-initiation not quantified
  14. 2009 High

    Completed the structural mechanism of initiation, defining B-linker (DNA opening), B-reader (start-site scanning), and the displacement logic that triggers TFIIB release.

    Evidence Pol II–TFIIB crystal structures at 4.3 and 3.8 Å with functional analysis

    PMID:19820686 PMID:19965383

    Open questions at the time
    • State with nascent RNA not yet captured
    • Allosteric activation of synthesis only inferred
  15. 2010 High

    Connected TFIIB to 3′-end processing through serine-65 phosphorylation that controls CstF/CPSF recruitment, mechanistically coupling initiation and termination.

    Evidence phospho-site mapping, phospho-specific antibody, Co-IP, ChIP, and phospho-mutant transcription assays

    PMID:20226668

    Open questions at the time
    • Kinase responsible for S65 phosphorylation not identified
    • Stoichiometry across the transcription cycle unknown
  16. 2012 High

    Provided the definitive multi-state structural model of TFIIB action from cleft closure and start-site scanning through RNA-driven displacement at ~12–13 nt.

    Evidence crystal structures of apo Pol II–TFIIB at 3.4 Å and an initially transcribing complex with 6-nt RNA, plus functional mutagenesis

    PMID:23151482

    Open questions at the time
    • Activator-induced conformational states not captured in this framework
    • Human-specific differences from yeast model not addressed
  17. 2016 High

    Showed TFIIB promoter binding is highly transient and stabilized only by Pol II–TFIIF, defining a kinetic checkpoint in PIC formation.

    Evidence single-molecule fluorescence imaging in reconstituted and live-cell systems

    PMID:27798851

    Open questions at the time
    • In vivo determinants of residence time not fully defined
    • Relationship of transient binding to bursting unclear
  18. 2022 High

    Quantified the genome-wide requirement for TFIIB in human cells, confirming it is the dominant determinant of Pol II promoter activity and revealing termination defects upon depletion.

    Evidence auxin-inducible acute depletion with PRO-Seq across >70,000 promoters

    PMID:35947745

    Open questions at the time
    • Direct vs indirect termination effects not separated
    • Promoter features dictating differential sensitivity not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How activator-induced conformational changes in TFIIB are coupled to the kinetic stabilization checkpoint and to TFIIB's roles in looping and 3′ processing remains unresolved.
  • Structural basis of the activator-primed TFIIB state lacking
  • Mechanistic link between S65 phosphorylation, looping, and termination not unified
  • Kinase and regulatory inputs to TFIIB in human cells uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0140223 general transcription initiation factor activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4
Partners
FCP1GTF2A1GTF2F1POLR2ASSU72SUB1TBPVP16
Complex memberships
RNA polymerase II preinitiation complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 TFIIB (GTF2B) is a ~33 kDa polypeptide required for RNA polymerase II transcription initiation; its sequence contains a region with amino acid similarity to prokaryotic sigma factors, an imperfect direct repeat, and clusters of basic residues. It was purified to homogeneity and cloned, establishing it as an essential basal transcription factor. Protein purification, cDNA cloning, in vitro transcription assay Proceedings of the National Academy of Sciences of the United States of America High 1946368
1991 Recombinant TFIIB expressed in E. coli binds directly to the acidic activating region of VP16, demonstrating that an acidic transcriptional activator can directly contact TFIIB without additional adaptor proteins. TFIIB binding is a rate-limiting step during preinitiation complex assembly that is enhanced by an acidic activator. Affinity chromatography with recombinant proteins, in vitro transcription rate measurements Nature High 1922364
1992 The yeast SUA7 gene encodes a TFIIB homolog that is essential for normal transcription start site selection in vivo; sua7 mutations cause a downstream shift in initiation at cyc1 and ADH1 loci, establishing TFIIB as a determinant of start site selection. Genetic suppressor screen, molecular cloning, primer extension analysis, in vivo transcription start site mapping Cell High 1547497
1992 Members of the steroid hormone receptor superfamily (COUP-TF, estrogen receptor, progesterone receptor) directly interact with TFIIB (S300-II) via protein-protein interactions, identifying TFIIB as a direct target of steroid hormone receptor transactivators. Protein-protein interaction assay with recombinant proteins, affinity chromatography The Journal of biological chemistry Medium 1517211
1992 The N-terminal zinc-binding domain of TFIIB is required for recruitment of RNA polymerase II–TFIIF into the initiation complex, while the C-terminal repeat domain is required for interaction with TBP; mutagenesis of cysteine residues in the zinc finger abolishes Pol II recruitment without disrupting TBP binding, separating two functional domains. Site-directed mutagenesis, in vitro transcription, TBP-binding assay Proceedings of the National Academy of Sciences of the United States of America High 8516312
1993 The C-terminal domain of TFIIB (residues 106–316, TFIIBc) is sufficient for interaction with TBP on DNA but cannot recruit RNA polymerase II; the N-terminal domain is required for Pol II recruitment. TFIIBc arrests complex formation at the TBP-binding step and acts as a dominant negative. Limited proteolysis, gel mobility-shift assay, in vitro transcription Proceedings of the National Academy of Sciences of the United States of America High 8516311
1993 The C-terminal domain of TFIIB contains two functional regions: the direct-repeat domain sufficient for TBP-promoter complex interaction, and the N-terminal domain required for subsequent transcription initiation steps (Pol II recruitment). The C-terminal protease-resistant core also extends the TBP footprint on promoter DNA, suggesting a cryptic DNA-binding potential. Deletion mutagenesis, in vitro transcription, DNase I footprinting, protease sensitivity assay Molecular and cellular biology High 8413225
1993 Human thyroid hormone receptor beta (hTRβ) directly interacts with TFIIB at two contact sites: one in the N-terminus and one in the ligand-binding domain (LBD); each receptor region contacts distinct sites on TFIIB. Thyroid hormone significantly decreases the interaction of the LBD with TFIIB, suggesting receptor-mediated silencing operates through TFIIB. GST pulldown, deletion analysis, co-transfection/reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 8415616
1993 Drosophila TAFII40 (homolog of human hTAFII32) directly binds both the VP16 activation domain and basal factor TFIIB, suggesting a ternary activator–coactivator–basal factor interaction during activated transcription. In vitro protein-protein interaction assay, affinity chromatography Cell Medium 8221891
1993 ICP4 of herpes simplex virus forms a tripartite complex with TFIIB and TBP (or TFIID) on promoter DNA through direct protein-protein interactions, increasing the DNA-binding affinity of both ICP4 and TBP; this complex formation correlates with ICP4's ability to regulate gene expression. Gel retardation assay, DNase I footprinting, mutant analysis Journal of virology Medium 8392607
1994 YY1, TFIIB, and RNA polymerase II are sufficient to direct specific basal transcription on a supercoiled template in a TBP-independent manner, demonstrating that TFIIB can function in a minimal initiation complex where YY1 substitutes for TBP. Reconstituted in vitro transcription with purified components Cell High 8137426
1994 Mutations in the largest subunit of RNA polymerase II (sua8/RPB1) cause downstream shifts in transcription start site selection identical to sua7 (TFIIB) mutations, and sua7 sua8 double mutants show synthetic lethality and non-allelic non-complementation, establishing a functional interaction between TFIIB and Rpb1 in start site selection. Genetic suppressor screen, primer extension, synthetic lethality analysis Molecular and cellular biology High 8264591
1995 Crystal structure of the TFIIB–TBP–TATA-element ternary complex at 2.7 Å reveals: TFIIB core resembles cyclin A; TFIIB recognizes the preformed TBP-DNA complex through protein-protein and protein-DNA contacts; the N-terminal domain of core TFIIB forms the downstream surface of the complex, potentially fixing the transcription start site. X-ray crystallography at 2.7 Å resolution Nature High 7675079
1995 Solution NMR structure of the human TFIIB core domain (TFIIBc) reveals two direct repeats forming a pseudo-twofold symmetric alpha-helical fold similar to cyclin A; an extensive central basic surface including an amphipathic helix is critical for bridging TBP-DNA complex and RNA polymerase II. Multidimensional heteronuclear NMR spectroscopy Cell High 7671313
1995 TFIIB binds beneath the concave surface of TBP, contacting DNA both upstream and downstream of the TATA box, as determined by hydroxyl-radical footprinting and gel mobility-shift assays. TFIIB requires at least 7 bp of DNA on either side of the TATA box to form a stable complex. Hydroxyl-radical footprinting, gel mobility-shift assay Nature High 7637813
1995 Vitamin D receptor (VDR) directly binds TFIIB; cotransfection of VDR and TFIIB cooperatively activates a vitamin D-responsive reporter in P19 cells in a 1,25(OH)2D3-dependent manner, demonstrating functional interaction between TFIIB and a nuclear hormone receptor in vivo. GST fusion protein-protein binding assay, cotransfection reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 7878015
1995 The proline-rich activation domain of CTF1 selectively interacts with TFIIB (but not TBP) and facilitates TFIIB recruitment into TBP-DNA complexes during preinitiation complex assembly in both human and yeast systems. In vitro protein-protein interaction assay, TFIIB recruitment assay on immobilized templates Proceedings of the National Academy of Sciences of the United States of America Medium 8183887
1995 The Krüppel zinc-finger protein directly interacts with TFIIB to activate transcription when acting as a monomer from a proximal site; Kr dimers interact with TFIIEβ to repress transcription, demonstrating that the same transcription factor can activate or repress by engaging different components of the basal machinery. In vitro protein-protein interaction assay, in vitro transcription with purified components Nature Medium 7753175
1995 A 10-amino-acid cluster of basic residues in the N-terminal A/B domain of thyroid hormone receptor alpha (cT3Rα, amino acids 21–30) is essential for TFIIB interaction and T3-dependent transcriptional activation; the TFIIB region primarily involved maps to residues 178–201 (an amphipathic α-helix). Deletion and point mutagenesis, in vitro binding assay, reporter cotransfection Molecular and cellular biology Medium 7623841
1995 C/EBPα transactivation elements I and II (TE-I and TE-II) cooperatively mediate in vitro binding of C/EBPα to both TBP and TFIIB; the same amino acid motifs conserved in activating C/EBP family members are required for transcription activation in yeast and mammalian cells. In vitro binding assay, mutagenesis, transfection reporter assay in yeast and mammalian cells The EMBO journal Medium 7556073
1995 TFIIB NMR structure shows conformational variability of the free core domain compared to the TBP-DNA-bound crystal structure; interaction with VP16 activation domain or with the N-terminal zinc ribbon domain of TFIIB induces chemical shift changes concentrated in the first repeat and interrepeat linker, suggesting TFIIB is conformationally pliable and that VP16 promotes a conformation primed for TBP-DNA binding. NMR spectroscopy, 15N relaxation analysis, chemical shift perturbation mapping Biochemistry Medium 9609687
1996 High-resolution site-specific protein-DNA photocrosslinking of the human TBP–TFIIA–TFIIB–DNA quaternary complex reveals that TFIIA and TFIIB make more extensive interactions with promoter DNA than previously recognized; TBP, TFIIA, and TFIIB together surround two turns of promoter DNA, potentially forming a 'cylindrical clamp'. Site-specific protein-DNA photocrosslinking, UV crosslinking mapping Proceedings of the National Academy of Sciences of the United States of America High 8855228
1996 Yeast SSU71/TFG1 (the largest subunit of TFIIF) genetically interacts with TFIIB: ssu71-1 suppresses both the cold-sensitive phenotype and downstream start-site shift of sua7 (TFIIB) mutants, establishing a functional interaction between TFIIB and TFIIF large subunit in transcription start site selection. Genetic suppressor screen, molecular cloning, primer extension, sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 7724527
1996 The Rpb9 (Ssu73) subunit of RNA polymerase II genetically interacts with TFIIB (sua7-1): rpb9/ssu73-1 suppresses the cold-sensitive growth phenotype and downstream start-site shift of sua7-1, identifying the C-terminus of Rpb9 as a functional partner of TFIIB in start site selection. Genetic suppressor analysis, allele sequencing, primer extension Nucleic acids research Medium 8692696
1997 TBP residue Leu-189 (in the second stirrup-like loop) is specifically required for TFIIB interaction, distinct from residues (Lys-133, Lys-145, Lys-151) required for TFIIA and NC2 (Dr1) interactions, defining a specific TFIIB-binding surface on TBP. NC2 is shown to be identical to the negative cofactor Dr1. TBP mutant analysis, in vitro transcription, protein-protein interaction assays The Journal of biological chemistry Medium 7738039
1997 Altered-specificity TBP–TFIIB interaction array demonstrates that many activators use the known TBP–TFIIB interaction to stimulate transcription in human cells, while the glutamine-rich activation domain of Sp1 activates transcription independently of this interaction. Engineered altered-specificity TATA-TBP-TFIIB array, transfection reporter assay Science High 9012349
1998 Hepatitis B virus pX protein co-immunoprecipitates with TFIIB from nuclear extracts and interacts with TFIIB in vivo. TFIIB mutants unable to bind TBP block pX activity, while TFIIB mutants unable to bind Pol II retain activity that is restored by pX, indicating pX acts as a molecular bridge between TFIIB and Pol II to coactivate transcription. Co-immunoprecipitation, TFIIB mutant analysis, in vivo and in vitro transcription assays Molecular and cellular biology High 9488473
1998 Two portions of the Fcp1p CTD phosphatase C-terminal region directly bind the first cyclin-like repeat in the core domain of TFIIB; the closely related KEFGK motif in RAP74 (TFIIF large subunit) also mediates Fcp1p interaction; mutation of this RAP74 motif causes synthetic phenotypes with fcp1 mutants. Deletion and point mutagenesis, direct binding assay, genetic synthetic lethality Molecular and cellular biology Medium 11003641
1998 The N-terminal region of yeast TFIIB contains two adjacent functional domains: a zinc ribbon fold required for stable RNAP II binding, and a highly conserved adjacent homology block required for transcription start site selection, demonstrating these are separable functions. Site-directed mutagenesis, in vitro transcription, start site selection assay, TFIIB-Pol II complex formation assay The Journal of biological chemistry High 9651390
1998 The archaeal TFIIB homolog TFB (from Sulfolobus shibatae) mediates sequence-specific DNA interactions with the region flanking the A-box (TATA-like element) upstream of the promoter, contributing to promoter strength independently of TBP. Gel mobility shift, footprinting, in vitro transcription with promoter mutants Molecular cell Medium 9660923
1999 Yeast SUB1 was identified as a suppressor of TFIIB mutations (E62G, R78H); SUB1 directly binds TFIIB in vitro and inhibits formation of TBP-TFIIB-promoter complexes; allele-specific interactions with ssu72 and sub1 establish functional relationships among TFIIB, Ssu72, and Sub1 in start site selection. Genetic suppressor screen, in vitro protein binding, TBP-TFIIB-DNA complex formation assay, allele specificity analysis The EMBO journal / Genetics High 10511545 8617240
1999 A yeast TFIIB S53P substitution specifically impairs activator-dependent (Pho4- and Adr1-mediated) transcription without affecting basal transcription. Pho4 directly interacts with TFIIB in vitro, and this interaction is reduced by S53P. Pho4 binding induces a conformational change in TFIIB detectable by enhanced V8 protease sensitivity. Genetic screen, in vitro protein-protein interaction assay, protease sensitivity assay, reporter transcription assay Proceedings of the National Academy of Sciences of the United States of America High 10077585
1999 TFIIB mutations E62G and TATA box mutations severely impair transcription without large defects in preinitiation complex formation, demonstrating post-recruitment roles for TFIIB and the TATA box after factor recruitment to the promoter. Immobilized promoter assay, conditional mutant cell extracts, PIC assembly and activity measurement Genes & development High 9887099
2001 The TFIIB recognition element (BRE) upstream of the TATA box suppresses basal transcription; an activator can disrupt the TFIIB-BRE interaction within a promoter-bound complex, revealing a novel activator function in modulating core promoter recognition by TFIIB. Transcription assay with BRE-mutant promoters, protein-DNA footprinting, functional analyses Genes & development High 11711430
2003 Site-specific photocrosslinking and hydroxyl radical probing in the preinitiation complex reveal that the TFIIB zinc ribbon domain interacts with the Pol II Dock domain, overlapping the RNA exit point. In the full PIC (but not the smaller Pol II-TFIIB complex), the TFIIB linker and core domains are positioned over the central cleft and wall of Pol II. Site-specific photocrosslinking, directed hydroxyl radical probing, mutational analysis Molecular cell High 14536083
2004 Crystal structure of the Pol II–TFIIB complex at 4.5 Å reveals three key features: (1) the N-terminal zinc ribbon of TFIIB contacts the Pol II Dock domain near the RNA exit path; (2) the B-finger domain inserts into the Pol II active center; (3) the C-terminal domain interacts with both Pol II and TBP-promoter DNA to orient DNA for unwinding and transcription start. X-ray crystallography at 4.5 Å resolution Science High 14963322
2004 A core promoter element downstream of the TATA box (downstream BRE) is recognized by TFIIB through a DNA-binding domain distinct from the helix-turn-helix motif used for the upstream BRE; the two TFIIB-recognition elements cooperate in a promoter context-dependent manner. Promoter element mutagenesis, in vitro transcription, TFIIB DNA-binding assay Genes & development High 16230532
2004 Functional interaction between the TFIIB B-finger domain (R78C mutation) and the lobe domain of the Rpb2 subunit of RNA polymerase II is required for accurate transcription start site selection; the TFIIB R78C mutant supports initiation but yields altered abortive initiation products, and lobe/jaw mutations in Rpb2 suppress the TFIIB defect. Genetic suppressor analysis, in vitro transcription, run-on transcription, abortive initiation assay Molecular and cellular biology High 15082791
2005 Regardless of TATA box–start site spacing, the upstream transcription bubble edge forms 20 bp from the TATA box, expanding to 18 unwound bases before abrupt collapse (re-annealing) when RNA is ≥7 nt. Bubble collapse coincides with loss of TFIIH helicase requirement and suppresses pausing caused by the TFIIB B-finger within the complex, linking TFIIB B-finger displacement to promoter clearance. Promoter spacing mutagenesis, permanganate footprinting of transcription bubbles, quantitative elongation assay Molecular cell High 15989968
2007 TFIIB plays a transcription-independent role in gene looping: TFIIB crosslinks to both the promoter and the terminator of genes, and the TFIIB E62K mutation adversely affects looping at all genes tested. TFIIB association with the terminator depends on Ssu72 and is independent of TBP, while promoter association is unaffected. Chromatin immunoprecipitation (ChIP), chromosome conformation capture (3C), gene looping analysis with TFIIB mutants Molecular cell High 17803944
2007 Expansion of the TBP polyglutamine (polyQ) tract enhances the TBP–TFIIB interaction while reducing TBP dimerization; in SCA17 transgenic mice, increased TFIIB occupancy of the Hspb1 promoter is decreased, and overexpression of TFIIB alleviates mutant TBP-induced neuritic defects. Co-immunoprecipitation, ChIP, transgenic mouse model, lentiviral TFIIB overexpression Nature neuroscience Medium 17994014
2009 Crystal structure of the complete Pol II–TFIIB complex at 4.3 Å reveals the mechanism of transcription initiation: B-core domain binds the Pol II wall to position promoter DNA; B-linker binds the Pol II rudder/clamp to assist DNA opening; B-reader approaches the active site to scan for the start site; RNA synthesis and upstream DNA rewinding displace B-reader and B-linker respectively, triggering TFIIB release and elongation complex formation. X-ray crystallography at 4.3 Å, complementary functional analysis Nature High 19820686
2009 A new Pol II–TFIIB crystal structure at 3.8 Å reveals the C-terminal domain of TFIIB located above the active center cleft and the linker snaking toward the active center; this structure is complementary to the prior 4.5 Å structure, together revealing how TFIIB positions promoter DNA over the Pol II cleft. X-ray crystallography at 3.8 Å under different solution conditions Science High 19965383
2010 TFIIB is phosphorylated at serine 65 in vivo, and this modification is present in PICs. Serine 65 phosphorylation is required after RNA pol II CTD serine 5 phosphorylation but before productive initiation; it regulates TFIIB's interaction with the CstF-64 component of the 3′ cleavage/polyadenylation complex, directing CstF recruitment to terminators and CPSF/CstF recruitment to promoters. Phosphorylation site identification, phospho-specific antibody, co-immunoprecipitation, ChIP, functional transcription assay with phospho-mutants Current biology High 20226668
2011 TFIIF is not required for initiation or promoter clearance by RNA pol II. However, TFIIF stabilizes TFIIB within early elongation complexes; in the absence of TFIIF, TFIIB is lost immediately after initiation rather than at the normal +12–13 position. TFIIF depletion/phosphorylation (casein kinase 2), PIC assembly assay, TFIIB retention analysis in elongation complexes Proceedings of the National Academy of Sciences of the United States of America High 21896726
2011 RAP74 (large subunit of TFIIF) directly and independently binds TFIIB via its C-terminal region; RAP74 blocks TFIIB-RAP30 binding both by binding TFIIB and by binding RAP30, indicating that in the intact TFIIF complex, TFIIB-TFIIF contact is maintained exclusively through RAP74. Deletion mutagenesis, direct binding assay, in vitro transcription The Journal of biological chemistry Medium 8662660
2012 Crystal structures of the Pol II–TFIIB complex at 3.4 Å and of an initially transcribing complex with DNA template and 6-nt RNA reveal: (1) TFIIB partially closes the Pol II cleft to position DNA; (2) B-reader binds the DNA template strand upstream of the active site to assist start site selection; (3) TFIIB rearranges active-site residues and induces metal B binding; (4) TFIIB prevents DNA-RNA hybrid tilting during short RNA synthesis; (5) RNA beyond 12–13 nt clashes with TFIIB, triggering TFIIB displacement and elongation complex formation. X-ray crystallography at 3.4 Å (apo complex) and initially transcribing complex; functional mutational analysis Nature High 23151482
2016 Single-molecule imaging reveals that TFIIB binding to the promoter is highly transient (average residence time ~1.5 sec), whereas TFIID and TFIIA bind stably. Stable TFIIB association and PIC progression occur only in the presence of Pol II–TFIIF, defining a checkpoint where transient-to-stable TFIIB binding requires downstream factor recruitment. Single-molecule fluorescence imaging, live-cell imaging, reconstituted in vitro single-molecule transcription platform Genes & development High 27798851
2022 Rapid acute depletion of TFIIB in human cells (PRO-Seq) shows that TFIIB depletion has the largest general effect on Pol II promoter activity compared to TBP, TAF1, and XPB depletions; TFIIB depletion also correlates with apparent transcription termination defects downstream of genes, consistent with TFIIB's role in linking initiation and termination. Rapid acute protein depletion (auxin-inducible degron), precision nuclear run-on sequencing (PRO-Seq) at >70,000 promoters Nucleic acids research High 35947745

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Crystal structure of a TFIIB-TBP-TATA-element ternary complex. Nature 483 7675079
1993 Drosophila TAFII40 interacts with both a VP16 activation domain and the basal transcription factor TFIIB. Cell 390 8221891
1991 Binding of general transcription factor TFIIB to an acidic activating region. Nature 351 1922364
1993 Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proceedings of the National Academy of Sciences of the United States of America 329 8415616
1993 The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proceedings of the National Academy of Sciences of the United States of America 308 8434021
1992 Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). The Journal of biological chemistry 295 1517211
2004 Structural basis of transcription: an RNA polymerase II-TFIIB cocrystal at 4.5 Angstroms. Science (New York, N.Y.) 260 14963322
1994 TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA. Cell 253 8137426
2009 RNA polymerase II-TFIIB structure and mechanism of transcription initiation. Nature 247 19820686
1999 Intermediates in formation and activity of the RNA polymerase II preinitiation complex: holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB. Genes & development 208 9887099
1992 The yeast SUA7 gene encodes a homolog of human transcription factor TFIIB and is required for normal start site selection in vivo. Cell 193 1547497
1993 ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. Journal of virology 176 8392607
2009 Structure of an RNA polymerase II-TFIIB complex and the transcription initiation mechanism. Science (New York, N.Y.) 166 19965383
2001 Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation. Genes & development 165 11731483
1995 Transcription factor TFIIB and the vitamin D receptor cooperatively activate ligand-dependent transcription. Proceedings of the National Academy of Sciences of the United States of America 164 7878015
1992 A yeast TFIIB-related factor involved in RNA polymerase III transcription. Genes & development 164 1398071
2012 Structure and function of the initially transcribing RNA polymerase II-TFIIB complex. Nature 156 23151482
2007 A transcription-independent role for TFIIB in gene looping. Molecular cell 144 17803944
1992 PCF4 encodes an RNA polymerase III transcription factor with homology to TFIIB. Cell 139 1423589
2007 Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nature neuroscience 138 17994014
1995 CCAAT/enhancer binding protein-alpha amino acid motifs with dual TBP and TFIIB binding ability co-operate to activate transcription in both yeast and mammalian cells. The EMBO journal 137 7556073
1995 Control of transcription by Krüppel through interactions with TFIIB and TFIIE beta. Nature 130 7753175
1993 The human cytomegalovirus 86K immediate early (IE) 2 protein requires the basic region of the TATA-box binding protein (TBP) for binding, and interacts with TBP and transcription factor TFIIB via regions of IE2 required for transcriptional regulation. The Journal of general virology 125 8277274
1998 Sequence-specific DNA binding by the S. shibatae TFIIB homolog, TFB, and its effect on promoter strength. Molecular cell 120 9660923
1995 Solution structure of the C-terminal core domain of human TFIIB: similarity to cyclin A and interaction with TATA-binding protein. Cell 120 7671313
2005 A core promoter element downstream of the TATA box that is recognized by TFIIB. Genes & development 116 16230532
1998 Hepatitis B virus pX targets TFIIB in transcription coactivation. Molecular and cellular biology 115 9488473
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 Structure and function of a human transcription factor TFIIIB subunit that is evolutionarily conserved and contains both TFIIB- and high-mobility-group protein 2-related domains. Proceedings of the National Academy of Sciences of the United States of America 114 7624363
1993 Functional domains of transcription factor TFIIB. Proceedings of the National Academy of Sciences of the United States of America 114 8516312
1994 Proline-rich activator CTF1 targets the TFIIB assembly step during transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 113 8183887
2004 Mapping the location of TFIIB within the RNA polymerase II transcription preinitiation complex: a model for the structure of the PIC. Cell 110 15479635
2005 The role of the transcription bubble and TFIIB in promoter clearance by RNA polymerase II. Molecular cell 106 15989968
2003 Binding of TFIIB to RNA polymerase II: Mapping the binding site for the TFIIB zinc ribbon domain within the preinitiation complex. Molecular cell 103 14536083
1995 Molecular cloning and expression of the 32-kDa subunit of human TFIID reveals interactions with VP16 and TFIIB that mediate transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 103 7597030
1996 Yeast SUB1 is a suppressor of TFIIB mutations and has homology to the human co-activator PC4. The EMBO journal 101 8617240
1991 Sequence of general transcription factor TFIIB and relationships to other initiation factors. Proceedings of the National Academy of Sciences of the United States of America 99 1946368
1998 Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-beta enhanceosome in vitro. Proceedings of the National Academy of Sciences of the United States of America 95 9770462
1996 High-resolution mapping of nucleoprotein complexes by site-specific protein-DNA photocrosslinking: organization of the human TBP-TFIIA-TFIIB-DNA quaternary complex. Proceedings of the National Academy of Sciences of the United States of America 95 8855228
1995 A 10-amino-acid sequence in the N-terminal A/B domain of thyroid hormone receptor alpha is essential for transcriptional activation and interaction with the general transcription factor TFIIB. Molecular and cellular biology 94 7623841
1995 In vitro interaction of the human immunodeficiency virus type 1 Tat transactivator and the general transcription factor TFIIB with the cellular protein TAP. Journal of virology 93 7707528
1995 The Epstein-Barr virus nuclear protein 2 acidic domain can interact with TFIIB, TAF40, and RPA70 but not with TATA-binding protein. Journal of virology 91 7983760
1995 Model for binding of transcription factor TFIIB to the TBP-DNA complex. Nature 89 7637813
2015 Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. Cell 87 26638071
2004 Plant class B HSFs inhibit transcription and exhibit affinity for TFIIB and TBP. Plant molecular biology 86 15604728
1995 Bovine papillomavirus type 1 E2 transcriptional regulators directly bind two cellular transcription factors, TFIID and TFIIB. Journal of virology 85 7666533
1993 Delineation of two functional regions of transcription factor TFIIB. Proceedings of the National Academy of Sciences of the United States of America 84 8516311
1996 Two-dimensional crystallography of TFIIB- and IIE-RNA polymerase II complexes: implications for start site selection and initiation complex formation. Cell 81 8646784
1998 The N-terminal region of yeast TFIIB contains two adjacent functional domains involved in stable RNA polymerase II binding and transcription start site selection. The Journal of biological chemistry 79 9651390
1996 ADR1 activation domains contact the histone acetyltransferase GCN5 and the core transcriptional factor TFIIB. The Journal of biological chemistry 78 8943299
1999 Function of steroidogenic factor 1 domains in nuclear localization, transactivation, and interaction with transcription factor TFIIB and c-Jun. Molecular endocrinology (Baltimore, Md.) 76 10478848
1999 Mutational analysis of yeast TFIIB. A functional relationship between Ssu72 and Sub1/Tsp1 defined by allele-specific interactions with TFIIB. Genetics 76 10511545
1994 The sua8 suppressors of Saccharomyces cerevisiae encode replacements of conserved residues within the largest subunit of RNA polymerase II and affect transcription start site selection similarly to sua7 (TFIIB) mutations. Molecular and cellular biology 75 8264591
1993 Functional dissection of TFIIB domains required for TFIIB-TFIID-promoter complex formation and basal transcription activity. Nature 74 8515820
2007 TFIIB and the regulation of transcription by RNA polymerase II. Chromosoma 73 17593382
1994 Evidence for a protein domain superfamily shared by the cyclins, TFIIB and RB/p107. Nucleic acids research 73 8152925
1995 TATA-binding protein residues implicated in a functional interplay between negative cofactor NC2 (Dr1) and general factors TFIIA and TFIIB. The Journal of biological chemistry 69 7738039
2000 A motif shared by TFIIF and TFIIB mediates their interaction with the RNA polymerase II carboxy-terminal domain phosphatase Fcp1p in Saccharomyces cerevisiae. Molecular and cellular biology 65 11003641
1999 Specific interactions with TBP and TFIIB in vitro suggest that 14-3-3 proteins may participate in the regulation of transcription when part of a DNA binding complex. The Plant cell 64 10449590
1996 TFIIB-directed transcriptional activation by the orphan nuclear receptor hepatocyte nuclear factor 4. Molecular and cellular biology 64 8657158
2011 Yeast Rrn7 and human TAF1B are TFIIB-related RNA polymerase I general transcription factors. Science (New York, N.Y.) 62 21921198
2000 A novel subunit of yeast RNA polymerase III interacts with the TFIIB-related domain of TFIIIB70. Molecular and cellular biology 62 10611227
2010 Phosphorylation of TFIIB links transcription initiation and termination. Current biology : CB 61 20226668
1995 Identification of the gene (SSU71/TFG1) encoding the largest subunit of transcription factor TFIIF as a suppressor of a TFIIB mutation in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 61 7724527
2016 Rapid dynamics of general transcription factor TFIIB binding during preinitiation complex assembly revealed by single-molecule analysis. Genes & development 60 27798851
1998 Functional and structural organization of Brf, the TFIIB-related component of the RNA polymerase III transcription initiation complex. Molecular and cellular biology 58 9710642
1995 Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. Molecular and cellular biology 57 7791769
1996 Functional interaction between TFIIB and the Rpb9 (Ssu73) subunit of RNA polymerase II in Saccharomyces cerevisiae. Nucleic acids research 56 8692696
1996 Interferon regulatory factors and TFIIB cooperatively regulate interferon-responsive promoter activity in vivo and in vitro. Molecular and cellular biology 56 8887661
1999 Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain of the p300 coactivator. Molecular and cellular biology 55 10330164
1993 Potential RNA polymerase II-induced interactions of transcription factor TFIIB. Molecular and cellular biology 55 8413225
2007 Human Maf1 negatively regulates RNA polymerase III transcription via the TFIIB family members Brf1 and Brf2. International journal of biological sciences 54 17505538
2001 Activator-mediated disruption of sequence-specific DNA contacts by the general transcription factor TFIIB. Genes & development 54 11711430
1995 Interaction of Oct-1 with TFIIB. Implications for a novel response elicited through the proximal octamer site of the lipoprotein lipase promoter. The Journal of biological chemistry 54 7642649
1998 Functional interaction of the bovine papillomavirus E2 transactivation domain with TFIIB. Journal of virology 53 9444994
1998 The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB. The Journal of biological chemistry 53 9722567
1995 Reversal of in vitro p53 squelching by both TFIIB and TFIID. Molecular and cellular biology 53 7565799
1997 Mutational analysis of the D1/E1 core helices and the conserved N-terminal region of yeast transcription factor IIB (TFIIB): identification of an N-terminal mutant that stabilizes TATA-binding protein-TFIIB-DNA complexes. Molecular and cellular biology 51 9372909
2011 TAF1B is a TFIIB-like component of the basal transcription machinery for RNA polymerase I. Science (New York, N.Y.) 50 21921199
2011 Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB. Proceedings of the National Academy of Sciences of the United States of America 48 21502537
1995 Molecular cloning of the transcription factor TFIIB homolog from Sulfolobus shibatae. Proceedings of the National Academy of Sciences of the United States of America 48 7597084
2011 Transcription factor TFIIF is not required for initiation by RNA polymerase II, but it is essential to stabilize transcription factor TFIIB in early elongation complexes. Proceedings of the National Academy of Sciences of the United States of America 47 21896726
2006 A TFIIB-like protein is indispensable for spliced leader RNA gene transcription in Trypanosoma brucei. Nucleic acids research 47 16554554
1996 RNA polymerase II-associated protein (RAP) 74 binds transcription factor (TF) IIB and blocks TFIIB-RAP30 binding. The Journal of biological chemistry 46 8662660
2000 Alleviation of human papillomavirus E2-mediated transcriptional repression via formation of a TATA binding protein (or TFIID)-TFIIB-RNA polymerase II-TFIIF preinitiation complex. Molecular and cellular biology 43 10594014
2014 Plant homeodomain-leucine zipper I transcription factors exhibit different functional AHA motifs that selectively interact with TBP or/and TFIIB. Plant cell reports 42 24531799
1999 An activation-specific role for transcription factor TFIIB in vivo. Proceedings of the National Academy of Sciences of the United States of America 42 10077585
1998 Human general transcription factor TFIIB: conformational variability and interaction with VP16 activation domain. Biochemistry 41 9609687
1997 A tetratricopeptide repeat mutation in yeast transcription factor IIIC131 (TFIIIC131) facilitates recruitment of TFIIB-related factor TFIIIB70. Molecular and cellular biology 41 9372943
1992 Activation of RNA polymerase II transcription by the specific DNA-binding protein LSF. Increased rate of binding of the basal promoter factor TFIIB. The Journal of biological chemistry 41 1313810
1992 Isolation and characterization of a cDNA encoding Drosophila transcription factor TFIIB. Proceedings of the National Academy of Sciences of the United States of America 41 1557390
1999 Expression and heat-responsive regulation of a TFIIB homologue from the archaeon Haloferax volcanii. Molecular microbiology 40 10476041
2022 Differential dependencies of human RNA polymerase II promoters on TBP, TAF1, TFIIB and XPB. Nucleic acids research 39 35947745
1997 Selective use of TBP and TFIIB revealed by a TATA-TBP-TFIIB array with altered specificity. Science (New York, N.Y.) 39 9012349
2008 The plant-specific TFIIB-related protein, pBrp, is a general transcription factor for RNA polymerase I. The EMBO journal 38 18668124
2004 Functional interaction between TFIIB and the Rpb2 subunit of RNA polymerase II: implications for the mechanism of transcription initiation. Molecular and cellular biology 38 15082791
2006 A divergent transcription factor TFIIB in trypanosomes is required for RNA polymerase II-dependent spliced leader RNA transcription and cell viability. Eukaryotic cell 37 16467470
2003 Repression of the luteinizing hormone receptor gene promoter by cross talk among EAR3/COUP-TFI, Sp1/Sp3, and TFIIB. Molecular and cellular biology 37 12972613
1997 Basal transcription factors TBP and TFIIB and the viral coactivator E1A 13S bind with distinct affinities and kinetics to the transactivation domain of NF-kappaB p65. Nucleic acids research 37 9023117
1995 In vitro association between the Jun protein family and the general transcription factors, TBP and TFIIB. The Biochemical journal 37 7848298

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