Disease relevance of GTF2B

• The N-terminal domain of RAP74 (minimally aa 1 to 172) is sufficient to deliver pol II into a complex formed on the adenovirus major late promoter with the TATA-binding protein, TFIIB, and RAP30 [1].
• Antibodies to basal transcription factors TATA-binding protein and TFIIB, but not TFIIIC, inhibited HTLV-I OTU transcription [2].
• Transcriptional activators such as the herpes simplex virus VP16 facilitate this complex formation through conformational activation of TFIIB, a focal molecule of transcriptional initiation and activation [3].
• When the general transcription factors (GTFs) were added in the assay, NC enhances NF-kappaB, Sp1, and TFIIB-induced HIV-1 LTR-directed RNA transcription [4].
• In P19 embryonal carcinoma cells cotransfection of VDR and TFIIB cooperatively activated reporter transcription, while each factor alone gave very low to no activation [5].

High impact information on GTF2B

• Mapping the location of TFIIB within the RNA polymerase II transcription preinitiation complex: a model for the structure of the PIC [6].
• TFIIB greatly accelerates formation of a bent TFIIB-TBP-TATA box complex, and the inhibitory DNA binding surface of TBP contributes to the cooperativity of binding to TFIIB [7].
• Solution structure of the C-terminal core domain of human TFIIB: similarity to cyclin A and interaction with TATA-binding protein [8].
• Abortive initiation assays revealed that TATA-binding protein, transcription factors TFIIB and TFIIF, and pol II were necessary and sufficient to form functional initiation complexes on both linear and supercoiled templates [9].
• We have identified previously two transcription factors, COUP (chicken ovalbumin upstream promoter) and S300-II, from HeLa cell nuclear extracts [10].

Chemical compound and disease context of GTF2B

• The acidic activation domain of the Epstein-Barr virus transcription factor R interacts in vitro with both TBP and TFIIB and is cell-specifically potentiated by a proline-rich region [11].
• Human transcription factor IIB (TFIIB) was discovered to be decreased on the 3rd day after the cells had been treated with retinoic acid and increased by phorbol 12-myristate 13-acetate, which stimulated the proliferation of human hepatocellular carcinoma cells [12].

Biological context of GTF2B

• TFIIB contains a region with amino acid sequence similarity to a highly conserved region of prokaryotic sigma factors [13].
• This "synthetic lethal" effect is not observed with E188A, suggesting that the previously described role of L189 in transcriptional activation may be related to its location on the DNA-binding surface and not to its interaction with TFIIB [14].
• Furthermore, we demonstrate interaction of TFIIB with Sp1/Sp3 at the Sp1(I) site besides its association with EAR3 and the TATA-less core promoter region [15].
• Conversely, the L189A mutation, which has the mildest effect on the interaction with TFIIB (10-fold), can abolish transcriptional activation and cell viability when combined with mutations on the DNA-binding surface [14].
• According to solution and mutagenesis studies, the multiple domains of RAP30 and RAP74 bind PolII, TFIIB, TAF250 and DNA in interactions that are essential for transcription initiation and elongation [16].

Anatomical context of GTF2B

• One serum, which strongly inhibited transcription in a cell-free system, was shown to contain antibodies directed against human TFIIB [17].
• TFIIB-directed transcriptional activation by the orphan nuclear receptor hepatocyte nuclear factor 4 [18].
• Likewise, GST-E2TA bound TFIID and TFIIB present in a nuclear extract from the human cervical cancer-derived cell line, HeLa [19].
• In contrast, transfection of NIH 3T3 cells generated strong reporter activation by 1,25(OH)2D3 in the presence of VDR alone, and cotransfection of TFIIB led to specific dose-dependent repression of reporter activity [5].
• Expressing amino acids 1-124 of human TFIIB (N-TFIIB) in COS-7 cells or in osteoblastic ROS17/2.8 cells effectively suppressed 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-induced transcription, but had no effect on basal or glucocorticoid-activated transcription [20].

Associations of GTF2B with chemical compounds

• Purified S300-II is also required for steroid receptor-activated transcription [21].
• Our findings suggest that there is a regulatory pathway controlling acetylation of TFIIB, and they link acetyl-CoA with basal gene transcription [22].
• The first step involves AF-2-independent recruitment of TFIIB to the promoter complex; the second step is AF-2 dependent and entails entry of preinitiation complex components acting downstream of TFIIB [18].
• We have shown that the human general transcriptional factor IB (TFIIB) auto-acetylates specifically at lysine 238 in the presence of acetyl coenzyme A in vitro [23].
• The sugar residues protected from hydroxyl-radical cleavage by the TFIIB-TBP complex were mapped on the crystal-structure model of the TBP-DNA complex [24].

Physical interactions of GTF2B

• Second, unlike yeast TBP, human TBP can use a shared surface to interact with two different TFIIB family members--TFIIB and Brf2--to initiate transcription by different RNA polymerases [25].
• In vitro protein-protein interaction assays reveal that as observed with Drosophila TAFII40, hTAFII32 interacts with the C-terminal 39-amino acid activation domain of the acidic transactivator viral protein 16 (VP16) as well as with the general transcription factor TFIIB [26].
• TFIIB binds to an overlapping region of RAP30, localized to amino acids 1-176 (amino acids 27-152 comprise a minimal binding region) [27].
• The C-terminal region of RAP74 (amino acids 358-517) binds directly and independently to TFIIB [27].
• RNA polymerase II-associated protein (RAP) 74 binds transcription factor (TF) IIB and blocks TFIIB-RAP30 binding [27].

Regulatory relationships of GTF2B

• CTF1-enhanced TFIIB recruitment was observed in both human and yeast systems [28].
• Simian virus 40 large T antigen interacts with human TFIIB-related factor and small nuclear RNA-activating protein complex for transcriptional activation of TATA-containing polymerase III promoters [29].

Other interactions of GTF2B

• When only TBP, TFIIB, and pol II were present in the reaction, the more negatively supercoiled the IgH template DNA was, the more active the transcription [30].
• Mutants were tested for accurate transcriptional activity, RAP74 binding, and TFIIB binding [27].
• Although S300-II does not bind DNA selectively, it stabilizes the binding of COUP-TF to its ciselement (Tsai, S. Y., Sagami, I., Wang, H., Tsai, M.-J., and O'Malley, B. W. (1987) Cell 50, 701-709) [21].
• Interestingly, a truncated estrogen receptor construct containing only the N-terminal transcription activation function 1 did not interact with S300-II/TFIIB in our assay, revealing that individual transcription activation functions of a single steroid hormone receptor may contact different targets [21].
• However, in the reverse titration, with very high mole ratios of HMG-1 present, TFIIB is not dissociated off and a complex is formed that contains all factors [31].

Analytical, diagnostic and therapeutic context of GTF2B

• Functional dissection of TFIIB domains required for TFIIB-TFIID-promoter complex formation and basal transcription activity [32].
• Affinity chromatography with immobilized deletion mutants of ER maps a TFIIB interaction region that encompasses the DNA-binding domain [33].
• Two other charged replacements, G363E and G363K, were constructed by site-directed mutagenesis and suppress both TFIIB E62K and Rpb1 N445S, whereas neither G363A nor G363P exhibited any effect [34].
• We show that activators function during at least two stages of preinitiation complex assembly: first, to recruit the general transcription factor TFIIB, and then at a second step, after TFIIB entry [35].
• The isomerized complex supports both binding of TFIIB in gel mobility shift assays and activated transcription in heat-treated nuclear extracts, even after removal of ZEBRA [36].

References