Affinage

GTF2B

Transcription initiation factor IIB · UniProt Q00403

Length
316 aa
Mass
34.8 kDa
Annotated
2026-04-28
100 papers in source corpus 49 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GTF2B (TFIIB) is a general transcription factor essential for RNA polymerase II preinitiation complex (PIC) assembly, transcription start site selection, promoter clearance, and coupling of initiation to termination. Its C-terminal cyclin-fold core domain recognizes TBP on promoter DNA and contacts flanking BRE elements upstream and downstream of the TATA box, while its N-terminal zinc ribbon domain binds the Pol II dock domain to recruit Pol II–TFIIF; within the PIC, the B-linker assists DNA strand opening and the B-reader positions the template strand for start site selection, with TFIIB displacement triggered by clash with the growing RNA transcript at 12–13 nucleotides to permit elongation (PMID:19820686, PMID:23151482, PMID:9660923, PMID:16230532). TFIIB is a direct target of diverse transcriptional activators—including acidic (VP16), proline-rich (CTF1), and nuclear receptor classes—whose binding induces conformational changes that modulate TFIIB recruitment and PIC formation (PMID:1922364, PMID:1517211, PMID:10077585, PMID:7583100). Beyond initiation, TFIIB is phosphorylated at Ser65 within the PIC, linking it to CstF-mediated 3′-end processing, and participates in gene loop formation between promoters and terminators via interaction with the Ssu72 phosphatase, establishing TFIIB as a physical and functional bridge coupling transcription initiation to termination (PMID:20226668, PMID:17803944, PMID:35947745).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Cloning and purification of TFIIB revealed it as a single-polypeptide general transcription factor with structural homology to bacterial sigma factors and direct repeat architecture, establishing it as a bridge between TFIID and RNA Pol II, and identifying it as a direct target of acidic activators like VP16.

    Evidence cDNA cloning, sequence analysis, recombinant protein affinity chromatography with VP16

    PMID:1922364 PMID:1946368

    Open questions at the time
    • No structural model of TFIIB at this stage
    • Mechanism of how activator binding stimulates PIC assembly unknown
  2. 1992 High

    Yeast genetics showed that TFIIB (SUA7) is a determinant of transcription start site selection in vivo, shifting the understanding of TFIIB from a passive scaffold to an active participant in positioning the initiation site.

    Evidence Genetic suppressor screen at cyc1 and ADH1 loci; primer extension mapping of start sites in sua7 mutants

    PMID:1547497

    Open questions at the time
    • Structural basis of start site selection unknown
    • Whether mammalian TFIIB performs the same function unclear
  3. 1993 High

    Domain dissection established that TFIIB has a bipartite architecture: the C-terminal core binds TBP–DNA while the N-terminal zinc-finger region recruits RNA Pol II–TFIIF, resolving how one factor bridges promoter recognition and polymerase recruitment.

    Evidence Limited proteolysis, cysteine mutagenesis, gel-shift and in vitro transcription assays

    PMID:8413225 PMID:8515820 PMID:8516312

    Open questions at the time
    • Atomic resolution structure lacking
    • Role of the linker between domains unknown
  4. 1995 High

    Crystal and NMR structures of the TFIIB core domain and the TFIIB–TBP–TATA ternary complex revealed the cyclin-fold architecture and how TFIIB contacts DNA both upstream and downstream of the TATA box, providing the first atomic framework for understanding promoter recognition and start site positioning.

    Evidence X-ray crystallography at 2.7 Å; multidimensional NMR spectroscopy; hydroxyl-radical footprinting

    PMID:7637813 PMID:7671313 PMID:7675079

    Open questions at the time
    • Structure of TFIIB with Pol II not yet determined
    • BRE sequence specificity not formally defined
  5. 1995 High

    TFIIB was shown to be a convergent target of diverse activator classes (acidic, proline-rich, glutamine-rich) and nuclear receptors, with activator binding inducing conformational changes on a defined regulatory surface, establishing TFIIB recruitment as a universal rate-limiting step in transcriptional activation.

    Evidence In vitro transcription with TFIIB mutants; protease footprinting; protein-protein binding with VDR, T3Rα, CTF1, VP16

    PMID:7583100 PMID:7597078 PMID:7878015 PMID:8183887

    Open questions at the time
    • Structural basis of activator-induced conformational change unresolved
    • Whether all promoters depend equally on TFIIB recruitment unknown
  6. 1998 High

    TFIIB was found to recognize a specific upstream DNA element (BRE) as a codeterminant of promoter strength, and the N-terminal zinc ribbon and adjacent B-finger were shown to have separable functions in Pol II binding versus start site selection, refining the functional map of TFIIB's N-terminal region.

    Evidence In vitro binding and transcription with promoter and TFIIB mutants; yeast mutagenesis

    PMID:9651390 PMID:9660923

    Open questions at the time
    • Downstream BRE not yet identified
    • Mechanism of B-finger action in start site selection unknown at atomic level
  7. 2004 High

    The first crystal structure of the Pol II–TFIIB complex revealed three key contacts: the zinc ribbon at the Pol II dock domain, the B-finger inserted into the active center, and the C-terminal domain orienting promoter DNA, providing a structural explanation for TFIIB's multifunctional role in initiation.

    Evidence X-ray crystallography at 4.5 Å; site-specific photocrosslinking; directed hydroxyl radical probing

    PMID:14536083 PMID:14963322

    Open questions at the time
    • Resolution insufficient to define B-reader contacts with template strand
    • Initially transcribing complex structure lacking
  8. 2005 High

    A downstream BRE (BREd) was identified, showing TFIIB recognizes elements flanking both sides of the TATA box through two independent DNA-binding motifs, and the B-finger was shown to cause pausing at +7–9, with bubble collapse marking the promoter clearance transition.

    Evidence In vitro transcription with varied promoter spacing; bubble mapping; BREd mutagenesis

    PMID:15989968 PMID:16230532

    Open questions at the time
    • How BREu and BREd cooperate structurally in the full PIC unclear
    • Whether bubble collapse is the sole trigger for TFIIB release unknown
  9. 2007 High

    TFIIB was found to occupy both promoter and terminator regions of genes and to be required for gene loop formation in an Ssu72-dependent manner, revealing a transcription-independent structural role that physically links initiation and termination.

    Evidence ChIP and chromosome conformation capture (3C) in yeast with TFIIB and Ssu72 mutants

    PMID:17803944

    Open questions at the time
    • Whether gene looping occurs in mammalian cells via TFIIB unknown
    • Molecular contacts at the terminator not defined
  10. 2009 High

    Higher-resolution Pol II–TFIIB crystal structures resolved the complete mechanism: B-linker assists DNA opening by binding the Pol II rudder, B-reader assists template scanning and TSS recognition, and RNA synthesis plus DNA rewinding displace B-reader/B-linker to trigger TFIIB release.

    Evidence X-ray crystallography at 4.3 Å and 3.8 Å with functional mutagenesis

    PMID:19820686 PMID:19965383

    Open questions at the time
    • Structure of an actively transcribing complex with nascent RNA still needed
    • Role of TFIIF in stabilizing TFIIB during this process not structurally resolved
  11. 2010 High

    Phosphorylation of TFIIB at Ser65 within the PIC was shown to regulate interaction with CstF-64, directing 3′-end processing machinery recruitment and providing a molecular mechanism linking promoter-bound TFIIB to termination.

    Evidence In vivo phosphorylation mapping; ChIP; co-immunoprecipitation with CstF-64

    PMID:20226668

    Open questions at the time
    • Kinase responsible for Ser65 phosphorylation not identified
    • Whether this modification is universal across all Pol II genes unknown
  12. 2012 High

    Crystal structures of the initially transcribing complex revealed that the B-reader binds template strand upstream of the active site for TSS positioning, directs RNA to the exit tunnel after 6 nt, and is displaced by clash with the growing RNA at 12–13 nt, completing the structural narrative of TFIIB function from initiation through clearance.

    Evidence X-ray crystallography at 3.4 Å of Pol II–TFIIB with DNA template and 6-nt RNA; mutagenesis

    PMID:23151482

    Open questions at the time
    • Full PIC structure with all GTFs not yet available at this resolution
    • Dynamics of TFIIB displacement in vivo not directly measured
  13. 2016 High

    Single-molecule and genome-wide studies showed that TFIIB promoter binding is highly transient (~1.5 s) until stabilized by Pol II–TFIIF arrival, and that Mediator contacts TFIIB through Med10 to facilitate PIC assembly genome-wide in a promoter architecture-dependent manner.

    Evidence Single-molecule fluorescence microscopy; ChIP genome-wide; Med10 mutant analysis in vitro and in vivo

    PMID:27688401 PMID:27798851

    Open questions at the time
    • How Mediator–TFIIB interaction is regulated at individual promoters unclear
    • Structural basis of Med10–TFIIB contact unknown
  14. 2022 High

    Acute TFIIB depletion showed it has the largest effect on Pol II promoter activity among general transcription factors and confirmed termination defects downstream of genes, validating TFIIB's dual role in initiation and termination genome-wide in human cells.

    Evidence Auxin-induced degradation in HAP1 cells; PRO-seq genome-wide

    PMID:35947745

    Open questions at the time
    • Whether termination defects are direct consequences of lost gene looping or lost CstF recruitment not resolved
    • Promoter-specific dependencies on TFIIB not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the Ser65 kinase, the structural basis of gene loop formation at terminators, whether TFIIB displacement dynamics differ across promoter classes in vivo, and how Mediator–TFIIB and activator–TFIIB interactions are coordinated within the complete PIC.
  • Ser65 kinase identity unknown
  • Structural basis of TFIIB at terminators not determined
  • Complete human PIC structure with TFIIB at atomic resolution not available
  • In vivo single-molecule dynamics of TFIIB displacement during elongation transition not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-8953854 Metabolism of RNA 3
Partners
CSTF2MED10RAP30RAP74RPB1RPB2SSU72TBP
Complex memberships
RNA Polymerase II preinitiation complex (PIC)

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 TFIIB directly binds the acidic activating region of VP16 protein without requiring additional adaptor proteins, establishing TFIIB as a direct target of acidic activators and a rate-limiting step in preinitiation complex assembly. Affinity chromatography with recombinant bacterially expressed TFIIB; in vitro binding assays Nature High 1922364
1991 TFIIB contains a region with amino acid sequence similarity to bacterial sigma factors, consistent with an analogous role in promoter recognition; it also contains a large imperfect repeat and clusters of basic residues, suggesting it serves as a bridge between TFIID and RNA polymerase II during preinitiation complex assembly. cDNA cloning, sequencing, sequence homology analysis, purification to homogeneity Proceedings of the National Academy of Sciences of the United States of America High 1946368
1992 S300-II (TFIIB) directly interacts with members of the steroid hormone receptor superfamily (COUP-TF, estrogen receptor, progesterone receptor) via protein-protein interactions, independent of adaptor proteins, identifying TFIIB as a direct target of nuclear receptor transactivators. Recombinant protein-protein interaction assays with purified proteins The Journal of biological chemistry High 1517211
1992 The yeast SUA7 gene encodes a TFIIB homolog that is required for normal transcription start site selection in vivo; sua7 mutations cause downstream shifts in transcription initiation at multiple loci (cyc1, ADH1), establishing TFIIB's role in start site selection. Genetic suppressor screen, molecular cloning, primer extension analysis of transcripts Cell High 1547497
1993 TFIIB consists of two separable functional domains: the C-terminal core domain (TFIIBc) interacts with TBP-DNA complex, while the N-terminal domain is required for recruitment of RNA polymerase II-TFIIF into the initiation complex. Mutagenesis of cysteine residues in the N-terminal zinc finger blocks Pol II-TFIIF recruitment without impairing TBP binding. Limited proteolysis domain mapping; mutagenesis of cysteine codons; gel mobility-shift assays; in vitro transcription assays Proceedings of the National Academy of Sciences of the United States of America High 8515820 8516311 8516312
1993 Drosophila TAFII40 directly binds both the VP16 activation domain and TFIIB, suggesting a ternary interaction among activator, coactivator, and TFIIB. Antibodies against dTAFII40 inhibit GAL4-VP16 activation without affecting basal transcription. In vitro protein-protein interaction assays; affinity chromatography; antibody inhibition Cell High 8221891
1993 HSV ICP4 forms a tripartite complex with TFIIB and TBP/TFIID on promoter DNA containing TATA box and ICP4-binding site; protein-protein interactions among all three proteins increase the affinity of ICP4 and TBP for their respective binding sites. Gel retardation assays, DNase I footprinting, use of mutant ICP4 derivatives Journal of virology High 8392607
1993 TFIIB core (C-terminal domain) forms a compact, protease-resistant structure that retains TBP binding but cannot support transcription. The N-terminal region mediates direct interaction with RNA Pol II (in association with TFIIF), and RNA Pol II may induce a conformational change in TFIIB leading to cryptic DNA-binding activity. Limited proteolysis, in vitro transcription, gel mobility-shift, DNase I footprinting Molecular and cellular biology High 8413225
1994 Specific TFIIB mutations (sua7-1: E62K; sua7-2: E62K; sua7-3: R78C) define conserved residues adjacent to the zinc finger of TFIIB as critical determinants of transcription start site selection. Double-mutant analysis suggests an E62-R78 salt bridge as an important structural element in this domain. Site-directed mutagenesis, reciprocal charge-swap double mutants, in vivo suppressor analysis The Journal of biological chemistry High 7982976
1994 SUA8 mutations in the largest subunit of RNA polymerase II (RPB1) cause downstream shifts in transcription start site selection similar to sua7 (TFIIB) mutations; 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, molecular cloning, synthetic lethality analysis, transcript mapping Molecular and cellular biology High 8264591
1994 The proline-rich activation domain of CTF1 selectively interacts with TFIIB (but not TBP) and facilitates TFIIB recruitment to TBP-DNA complexes, demonstrating that different activator types can target TFIIB for preinitiation complex assembly. In vitro protein-protein interaction; gel retardation assays monitoring TFIIB recruitment Proceedings of the National Academy of Sciences of the United States of America High 8183887
1995 Crystal structure of the TFIIB/TBP/TATA-element ternary complex at 2.7 Å reveals that core TFIIB resembles cyclin A and recognizes the preformed TBP-DNA complex through protein-protein and protein-DNA interactions; the N-terminal domain of core TFIIB forms the downstream surface of the ternary complex, potentially fixing the transcription start site. X-ray crystallography at 2.7 Å resolution Nature High 7675079
1995 NMR structure of human TFIIB core domain (TFIIBc) reveals two direct repeats with similar alpha-helical folds (resembling cyclin A) conferring pseudo-twofold symmetry; an extensive central basic surface including an amphipathic alpha helix is critical for TFIIB function as a bridge between TBP-promoter complex and RNA Pol II. Multidimensional heteronuclear NMR spectroscopy Cell High 7671313
1995 Monomeric Drosophila Krüppel (Kr) activates transcription through interaction with TFIIB when acting near the basal promoter, whereas Kr dimers repress transcription through interaction with TFIIE beta. In vitro protein-protein interaction assays, in vitro transcription with purified factors Nature High 7753175
1995 VDR (vitamin D receptor) directly binds TFIIB via select protein domains; co-transfection of VDR and TFIIB cooperatively activates a 1,25(OH)2D3-responsive reporter in a ligand-dependent manner in P19 cells, demonstrating functional interaction between TFIIB and a nuclear hormone receptor in vivo. GST fusion protein-protein binding assays; cotransfection reporter assays Proceedings of the National Academy of Sciences of the United States of America High 7878015
1995 Hydroxyl-radical footprinting and gel mobility-shift assays reveal that TFIIB binds beneath the concave surface of TBP, contacting DNA both upstream and downstream of the TATA box; TFIIB requires at least 7 bp of DNA on either side of the TATA box to form a stable TFIIB-TBP-DNA complex. Gel mobility-shift assays, hydroxyl-radical footprinting mapped onto TBP-DNA crystal structure Nature High 7637813
1995 High-resolution protein-DNA photocrosslinking reveals TFIIA and TFIIB make more extensive interactions with promoter DNA than previously anticipated; TBP, TFIIA, and TFIIB together surround promoter DNA for two turns of the helix, forming a 'cylindrical clamp' effectively topologically linked to promoter DNA. Site-specific protein-DNA photocrosslinking in binary, ternary, and quaternary complexes Proceedings of the National Academy of Sciences of the United States of America High 8855228
1995 The N-terminal A/B domain (amino acids 21-30, containing a basic amino acid cluster) of thyroid hormone receptor alpha (T3Rα) is essential for transcriptional activation and directly interacts with TFIIB (residues 178-201); this interaction is required for T3Rα-mediated transcriptional activation. In vitro binding studies with recombinant proteins; deletion and mutagenesis analysis; transient transfection Molecular and cellular biology High 7623841
1995 Protease footprinting reveals two regions of TFIIB protected by the VP16 activation domain and one region protected by TAFII40 (overlapping with the VP16 site), defining a regulatory surface on TFIIB that serves as an interface for both activators and coactivators. Protease footprinting with broad-specificity proteases on 32P-labeled TFIIB Proceedings of the National Academy of Sciences of the United States of America High 7597078
1995 Diverse activators (acidic, proline-rich, glutamine-rich) fail to recruit mutant forms of TFIIB that cannot respond to activators, demonstrating that activator-mediated TFIIB recruitment is a central and universal step in transcriptional activation; TFIIB dissociates after each round of transcription, requiring reassembly for each reinitiation. In vitro transcription with TFIIB mutants; gel retardation assays for TFIIB recruitment Current biology : CB High 7583100
1996 RAP74 (large subunit of TFIIF) directly binds TFIIB through its C-terminal region, while RAP30 binds TFIIB at an overlapping region; RAP74 blocks TFIIB-RAP30 binding by simultaneously binding TFIIB and RAP30, indicating that when TFIIF is intact, TFIIB-TFIIF contact is maintained through RAP74. Deletion mutagenesis, in vitro binding assays, in vitro transcription The Journal of biological chemistry High 8662660
1996 IRF-1 and IRF-2 bind to TFIIB; IRF-1 and TFIIB cooperatively enhance ISRE promoter activity both in vitro and in vivo; this cooperation is independent of the TATA sequence but dependent on the initiator sequence (Inr) and is cell-type specific. In vitro protein binding assays; in vitro transcription; cotransfection reporter assays Molecular and cellular biology High 8887661
1996 The yeast SUB1 protein (homolog of human co-activator PC4) binds TFIIB in vitro and specifically inhibits TBP-TFIIB-promoter complex formation; overexpression of SUB1 suppresses TFIIB alleles E62G and R78H, suggesting SUB1 facilitates TFIIB release during transcription initiation. Genetic suppressor screen; in vitro binding assays; gel retardation for complex formation The EMBO journal High 8617240
1998 TFIIB directly interacts with HBV pX protein in vivo (co-immunoprecipitation from nuclear extracts); pX bridges an otherwise inefficient TFIIB-POLII interaction, using TFIIB as a molecular scaffold for transcriptional coactivation. Co-immunoprecipitation from nuclear extracts; TFIIB mutant analysis; in vitro and in vivo transcription assays Molecular and cellular biology High 9488473
1998 TFIIB mediates sequence-specific DNA binding by recognizing a defined element upstream of the TATA box (BRE), and this recognition cooperates with TBP-TATA binding as a codeterminant of promoter strength. Mutagenesis, in vitro binding assays, in vitro transcription Molecular cell High 9660923
1998 The N-terminal region of yeast TFIIB contains two separable adjacent functional domains: the zinc ribbon fold mediates stable RNA Pol II binding, while a highly conserved homology block C-terminal to the zinc ribbon controls transcription start site selection. Site-directed mutagenesis; in vitro transcription; start site selection assays in vitro and in vivo; pulldown assays with purified Pol II The Journal of biological chemistry High 9651390
1998 NMR analysis shows TFIIB core domain is conformationally flexible in solution; binding of the VP16 activation domain or the N-terminal zinc domain induces chemical shift changes in the first repeat and interrepeat linker of TFIIBc, suggesting TFIIB is pliable and can be modulated by activator interactions to prime binding to TBP-DNA complexes. 1H-15N NMR, backbone 15N relaxation measurements, comparison with crystal structure Biochemistry High 9609687
1999 Genetic epistasis in yeast establishes functional interactions among TFIIB, Ssu72, and Sub1 that are allele-specific and linked specifically to TFIIB alleles affecting transcription start site selection, placing Ssu72 and Sub1 in the same functional pathway as TFIIB for start site selection. Error-prone PCR mutagenesis library, genetic suppressor/enhancer analysis, allele-specificity testing Genetics High 10511545
1999 The TFIIB S53P mutation specifically impairs activation of PHO5 and ADH2 without affecting basal transcription; Pho4 directly interacts with TFIIB in vitro and induces a conformational change in TFIIB (detected by enhanced V8 protease sensitivity), suggesting certain activators function by inducing conformational changes in TFIIB. Yeast mutagenesis screen; in vitro binding assay; protease sensitivity assay; reporter gene analysis Proceedings of the National Academy of Sciences of the United States of America High 10077585
2000 Fcp1p (CTD phosphatase) directly binds the first cyclin-like repeat in the TFIIB core domain via a KEFGK motif shared by TFIIB and the RAP74 subunit of TFIIF; this interaction is functionally significant for transcriptional activation. Deletion/point mutagenesis of Fcp1p; direct binding assays; genetic synthetic phenotype analysis Molecular and cellular biology High 11003641
2001 The BRE (TFIIB recognition element) upstream of the TATA box suppresses basal transcription, and activator proteins can disrupt the TFIIB-BRE interaction within promoter-bound complexes, revealing a novel activator function in modulating core promoter recognition by TFIIB. In vitro transcription assays; protein-DNA interaction assays Genes & development High 11711430
2004 Crystal structure of RNA Pol II-TFIIB cocrystal at 4.5 Å reveals three functional features: the TFIIB zinc ribbon domain contacts the Pol II dock domain near the RNA exit path; the B-finger domain inserts into the Pol II active center; and the C-terminal domain orients promoter DNA for unwinding and transcription initiation. X-ray crystallography at 4.5 Å Science High 14963322
2003 Site-specific photocrosslinking and directed hydroxyl radical probing map the TFIIB zinc ribbon domain to the Pol II Dock domain surface overlapping the RNA exit point within the preinitiation complex, defining a general mechanism for TFIIB-like factor interaction with RNA polymerases. Site-specific photocrosslinking, directed hydroxyl radical probing, mutational analysis Molecular cell High 14536083
2004 Biochemical probes on TFIIB reveal that in full PICs (not in the smaller Pol II-TFIIB complex), TFIIB linker and core domains are positioned over the central cleft and wall of Pol II; TFIIF subunit Tfg1 is in close proximity to TFIIB B-finger, linker, and core domains, suggesting close cooperation between TFIIB and TFIIF during initiation. Site-specific chemical probing of TFIIB within the PIC Cell High 15479635
2004 Functional interaction between TFIIB and the Rpb2 subunit of RNA Pol II is established by suppressor genetics; the B-finger domain (R78C) of TFIIB functionally interacts with the lobe domain (G369S) of Rpb2 in start site selection; TFIIB R78C alters abortive initiation patterns without precluding initiation. Genetic suppressor screen; in vitro transcription; run-on transcription; abortive initiation assays Molecular and cellular biology High 15082791
2005 TFIIB defines a downstream core promoter element (BREd, distinct from the upstream BRE); two independent DNA-binding motifs in TFIIB recognize elements flanking the TATA box and cooperate in transcription regulation in a promoter context-dependent manner. In vitro transcription assays; protein-DNA binding assays; mutagenesis Genes & development High 16230532
2005 Regardless of TATA-to-start-site spacing, the upstream transcription bubble edge forms 20 bp from TATA; the B-finger of TFIIB causes pausing at +7 to +9 within the complex, and bubble collapse (reannealing of upstream ~8 bases when bubble reaches 18 bp and RNA is ≥7 nt) suppresses this pausing and marks the promoter clearance transition. In vitro transcription with systematically varied promoter spacing; bubble mapping; nucleotide depletion Molecular cell High 15989968
2007 TFIIB has a transcription-independent role in gene looping in yeast: TFIIB crosslinks to both promoter and terminator regions of genes; the E62K TFIIB mutation adversely affects looping at multiple genes; TFIIB association with the terminator is dependent on the Ssu72 component of the CPF 3' end processing complex and is independent of TBP. Chromatin immunoprecipitation (ChIP); chromosome conformation capture (3C); genetic analysis with TFIIB and Ssu72 mutants Molecular cell High 17803944
2007 Expansion of the polyglutamine tract in TBP (SCA17) enhances the TBP-TFIIB interaction while reducing TBP dimerization; this leads to decreased TFIIB occupancy of the Hspb1 promoter and downregulation of HSPB1 in SCA17 transgenic mice; overexpression of TFIIB alleviates mutant TBP-induced neuritic defects. Transgenic mouse model; co-immunoprecipitation; ChIP; neuritic defect rescue Nature neuroscience High 17994014
2009 Crystal structure of the complete Pol II-TFIIB complex at 4.3 Å reveals initiation mechanism: B-core domain binds Pol II wall to position promoter DNA over the active centre cleft; B-linker binds the Pol II rudder and clamp coiled-coil to assist DNA opening; B-reader approaches the active site to assist template strand scanning and TSS recognition; RNA synthesis and DNA rewinding displace B-reader and B-linker to trigger TFIIB release and elongation. X-ray crystallography at 4.3 Å; complementary functional mutagenesis data Nature High 19820686
2009 A 3.8 Å crystal structure of the Pol II-TFIIB complex reveals the C-terminal region of TFIIB positioned above the polymerase active center cleft, and the linker between N- and C-terminal regions snaking down toward the active center; together with the prior 4.5 Å structure, these define two distinct conformational states of TFIIB in the complex. X-ray crystallography at 3.8 Å Science High 19965383
2010 TFIIB is phosphorylated at serine 65 in vivo within preinitiation complexes; this phosphorylation occurs after RNA Pol II CTD serine 5 phosphorylation but before productive initiation; phospho-S65 TFIIB regulates interaction with CstF-64 (component of the CstF cleavage/polyadenylation complex), directing CstF recruitment to the terminator and linking promoter to terminator function. In vivo phosphorylation mapping; PIC assembly analysis; ChIP; co-immunoprecipitation with CstF-64 Current biology : CB High 20226668
2011 TFIIF is not required for RNA Pol II initiation or promoter clearance per se, but is essential for stabilizing TFIIB in early elongation complexes; without TFIIF, TFIIB can be lost immediately after initiation rather than at the normal +12 to +13 displacement point. Casein kinase 2 phosphorylation of TFIIF to generate TFIIF-depleted PICs; in vitro transcription; factor retention analysis Proceedings of the National Academy of Sciences of the United States of America High 21896726
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: the complete B-reader does not reach the active site but binds DNA template strand upstream to assist initiator recognition and TSS positioning; TFIIB rearranges active-site residues and induces metal B binding; TFIIB prevents tilting of the DNA-RNA hybrid; when RNA grows beyond 6 nt, the B-reader loop directs RNA to its exit tunnel; when RNA reaches 12-13 nt, it clashes with TFIIB, triggering TFIIB displacement and elongation complex formation. X-ray crystallography at 3.4 Å; initially transcribing complex structure; functional mutagenesis Nature High 23151482
2016 Single-molecule analysis reveals TFIIB binding to the promoter is highly transient (average residence time ~1.5 sec) when TFIID and TFIIA are present, but undergoes a transient-to-stable transition only in the presence of Pol II-TFIIF, establishing Pol II-TFIIF recruitment as a checkpoint for TFIIB stabilization in PIC assembly. Single-molecule fluorescence microscopy; live-cell imaging; in vitro reconstituted transcription system Genes & development High 27798851
2016 Mediator interacts with TFIIB through its middle module subunit Med10; this Mediator-TFIIB interaction has a global role in PIC assembly genome-wide, and the amplitude of Mediator's effect on PIC formation is dependent on promoter architecture (TATA elements, nucleosome occupancy). In vivo ChIP, in vitro PIC assembly assays, genome-wide analysis, Med10 mutant analysis Genes & development High 27688401
2022 Rapid acute depletion of TFIIB in HAP1 cells shows the largest general effect on RNA Pol II promoter activity among GTFs tested; TFIIB depletion also correlates with apparent transcription termination defects downstream of genes, consistent with its role in linking initiation and termination. Rapid auxin-induced depletion; precision nuclear run-on sequencing (PRO-Seq) genome-wide 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
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
2009 RNA polymerase II-TFIIB structure and mechanism of transcription initiation. Nature 246 19820686
1992 The yeast SUA7 gene encodes a homolog of human transcription factor TFIIB and is required for normal start site selection in vivo. Cell 192 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 164 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 155 23151482
2007 A transcription-independent role for TFIIB in gene looping. Molecular cell 144 17803944
1992 A suppressor of TBP mutations encodes an RNA polymerase III transcription factor with homology to TFIIB. Cell 142 1423590
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 Control of transcription by Krüppel through interactions with TFIIB and TFIIE beta. Nature 130 7753175
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 115 16230532
1998 Hepatitis B virus pX targets TFIIB in transcription coactivation. Molecular and cellular biology 115 9488473
1998 Transcriptional repression by the SMRT-mSin3 corepressor: multiple interactions, multiple mechanisms, and a potential role for TFIIB. Molecular and cellular biology 114 9710634
1993 Functional domains of transcription factor TFIIB. Proceedings of the National Academy of Sciences of the United States of America 114 8516312
1994 Characterization of sua7 mutations defines a domain of TFIIB involved in transcription start site selection in yeast. The Journal of biological chemistry 113 7982976
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
1996 The human immunodeficiency virus type 1 Vpr transactivator: cooperation with promoter-bound activator domains and binding to TFIIB. Journal of molecular biology 102 8800208
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 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 85 26638071
2004 Plant class B HSFs inhibit transcription and exhibit affinity for TFIIB and TBP. Plant molecular biology 85 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
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 78 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 75 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 74 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
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
1993 Transcriptional activation by the acidic domain of Vmw65 requires the integrity of the domain and involves additional determinants distinct from those necessary for TFIIB binding. Molecular and cellular biology 65 8395001
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
2016 Rapid dynamics of general transcription factor TFIIB binding during preinitiation complex assembly revealed by single-molecule analysis. Genes & development 60 27798851
1997 Synergistic and promoter-selective activation of transcription by recruitment of transcription factors TFIID and TFIIB. Proceedings of the National Academy of Sciences of the United States of America 60 9223310
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 60 7724527
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 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
1996 Functional interaction between TFIIB and the Rpb9 (Ssu73) subunit of RNA polymerase II in Saccharomyces cerevisiae. Nucleic acids research 55 8692696
1995 A role for activator-mediated TFIIB recruitment in diverse aspects of transcriptional regulation. Current biology : CB 55 7583100
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
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 50 9372909
2011 TAF1B is a TFIIB-like component of the basal transcription machinery for RNA polymerase I. Science (New York, N.Y.) 49 21921199
2001 Promoter-specific shifts in transcription initiation conferred by yeast TFIIB mutations are determined by the sequence in the immediate vicinity of the start sites. Molecular and cellular biology 49 11416123
1993 Transcription factor TFIIB sites important for interaction with promoter-bound TFIID. Science (New York, N.Y.) 49 8332911
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 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 47 21502537
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 46 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
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 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
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
2022 Differential dependencies of human RNA polymerase II promoters on TBP, TAF1, TFIIB and XPB. Nucleic acids research 37 35947745
2004 Functional interaction between TFIIB and the Rpb2 subunit of RNA polymerase II: implications for the mechanism of transcription initiation. Molecular and cellular biology 37 15082791
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
1997 A severely defective TATA-binding protein-TFIIB interaction does not preclude transcriptional activation in vivo. Molecular and cellular biology 37 9032260
1995 In vitro association between the Jun protein family and the general transcription factors, TBP and TFIIB. The Biochemical journal 37 7848298
1995 A direct interaction between a glutamine-rich activator and the N terminus of TFIIB can mediate transcriptional activation in vivo. Molecular and cellular biology 37 7891725
1997 Conserved interaction of the papillomavirus E2 transcriptional activator proteins with human and yeast TFIIB proteins. Journal of virology 36 9311902
2003 Interactions of SKIP/NCoA-62, TFIIB, and retinoid X receptor with vitamin D receptor helix H10 residues. The Journal of biological chemistry 35 12529369
2003 Transcription factor IIB (TFIIB)-related protein (pBrp), a plant-specific member of the TFIIB-related protein family. Molecular and cellular biology 35 12697827
1995 Protease footprinting reveals a surface on transcription factor TFIIB that serves as an interface for activators and coactivators. Proceedings of the National Academy of Sciences of the United States of America 34 7597078
2016 Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture. Genes & development 32 27688401