Disease relevance of GTF2I

• Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23 [1].
• These results demonstrate that USF1/USF2 and TFII-I interact cooperatively at the upstream RBEIII element and are necessary for the induction of latent HIV-1 in response to T-cell activation signals [2].
• TFII-I regulates induction of chromosomally integrated human immunodeficiency virus type 1 long terminal repeat in cooperation with USF [2].
• We show here that a novel factor (TFII-I) binds specifically to Inr elements, supports basal transcription from the adenovirus major late promoter and is immunologically related to the helix-loop-helix activator USF [3].
• A candidate X-linked mental retardation gene and the transcription initiation factor II-I (TFII-I) are components of a novel member of this family of complexes [4].

Psychiatry related information on GTF2I

• GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region [5].

High impact information on GTF2I

• As previously observed for the bHLH activator USF, Myc was found to interact cooperatively with TFII-I at both Inr and upstream E-box promoter elements [6].
• Furthermore, TBP bound cooperatively (with only TFII-I) to an Inr-containing TATA-less promoter, suggesting a means for activation of TATA-less promoters, which nonetheless require TFIID (refs 9-11) [7].
• Here we describe a novel pathway that requires an intact Inr and the Inr-binding factor TFII-I (ref. 3). Sequential addition of the general factors generated TFII-I-dependent preinitiation complexes different from those formed with TFIIA [7].
• Multifunctional transcription factor TFII-I has two spliced isoforms (Delta and beta) in murine fibroblasts [8].
• Opposing Functions of TFII-I Spliced Isoforms in Growth Factor-Induced Gene Expression [8].

Chemical compound and disease context of GTF2I

• Interaction between the B-block region of adenovirus VA1 DNA and the human RNA polymerase III transcription factor (TFIII) C2 was analyzed using a gel DNA-binding assay [9].

Biological context of GTF2I

• Therefore, the duplicated region containing GTF2I and GTF2IP1 respectively is located close to the deletion breakpoints and may predispose to unequal meiotic recombination between chromosome 7 homologs and/or to intrachromosomal rearrangements [10].
• Hemizygosity for GTF2I may also contribute to the WBS phenotype [10].
• Tyrosine phosphorylation of TFII-I can be regulated in a signal-dependent manner in various cell types [11].
• Furthermore, both TFII-I and MusTRD1 bind to similar but distinct sequences, which happen to conform with the initiator (Inr) consensus sequence [12].
• A human MusTRD (muscle TFII-I repeat domain (RD)-containing protein) isoform was originally identified in a yeast one-hybrid screen as a protein that binds the slow fibre-specific enhancer of the muscle gene troponin I slow [O'Mahoney, Guven, Lin, Joya, Robinson, Wade and Hardeman (1998) Mol. Cell. Biol. 18, 6641-6652] [13].

Anatomical context of GTF2I

• In B lymphocytes, Bruton's tyrosine kinase has been identified as a TFII-I tyrosine kinase [11].
• Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6 [14].
• We have previously shown that transcription factors TFII-I and USF interact with the beta-globin promoter in erythroid cells [15].
• Mutation of either Tyr248, Tyr357, or Tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type BAP/TFII-I in transfected COS-7 cells, consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation [16].
• Transient-transfection assays demonstrate that TFII-I transactivates the RSV LTR from ca. fourfold (basal) to ca. sevenfold (enhanced) in both human and natural host cell lines [17].

Associations of GTF2I with chemical compounds

• TFII-I is a transcription factor that shuttles between the cytoplasm and nucleus and is regulated by serine and tyrosine phosphorylation [11].
• Repression by BRG1 required the cyclic AMP response element of the c-fos promoter but not nearby binding sites for Sp1, YY1, or TFII-I [18].
• Here we demonstrate that TFII-I is phosphorylated in vivo at serine/threonine and tyrosine residues in the absence of any apparent extracellular signals [19].
• PKG Ibeta, but not Ialpha, binds to the general transcriptional regulator TFII-I and the inositol 1,4,5-trisphosphate receptor-associated PKG substrate IRAG [20].
• Secondly, these results are also confirmed by the anisotropy of the self-diffusion tensor of the water molecule measured by (1)H Pulsed Gradient Spin Echo NMR [21].

Physical interactions of GTF2I

• We demonstrated that TFII-I binds to both the Inr and to three regulatory E boxes in the human VEGFR-2 promoter [22].
• In an immunoaffinity purification using anti-HDAC3, transcription factor TFII-I copurified with HDAC3 [23].
• Using a combination of site-directed mutagenesis and in vitro binding assays, we identified a group of acidic amino acids in the N-terminal leucine zipper dimerization domain of PKG Ibeta required for its binding to both TFII-I and IRAG [20].
• These differ in size from polypeptides in known general initiation factors, including the initiator-binding factor (TFII-I) which shares some promoter binding characteristics with TFIID [24].
• NF-kappa B homodimer binding within the HIV-1 initiator region and interactions with TFII-I [25].

Regulatory relationships of GTF2I

• We found that TFII-I is capable of acting at both basal and regulatory sites in one promoter and that the human VEGFR-2 promoter is functionally counter-regulated by TFII-I and TFII-IRD1 [22].
• Ectopic expression of wild-type Btk enhances TFII-I-mediated transcriptional activation and its tyrosine phosphorylation in transient-transfection assays [26].
• Inhibition of ACE by TFII-I requires phosphotyrosine residues that engage the SH2 (Src-homology 2) domains of phospholipase C-g (PLC-g) and an interrupted, pleckstrin homology (PH)-like domain that binds the split PH domain of PLC-g. Our observations suggest a model in which TFII-I suppresses ACE by competing with TRPC3 for binding to PLC-g [27].
• Phosphoproteome profiling of transforming growth factor (TGF)-beta signaling: abrogation of TGFbeta1-dependent phosphorylation of transcription factor-II-I (TFII-I) enhances cooperation of TFII-I and Smad3 in transcription [28].
• However, TFII-I is heat-inactivated at temperatures lower than that required to inactivate TFIID [29].

Other interactions of GTF2I

• We speculate that GTF2I is derived from GTF2IRD1 as a result of local duplication and the further evolution of its structure was associated with its functional specialization [30].
• The comparison of GTF2I and GTF2IRD2 genes revealed two distinct regions of homology, indicating that the helix-loop-helix domain structure of the GTF2IRD2 gene has been generated by two independent genomic duplications [30].
• In these cases, deletion breakpoints were mapped at several sites within the recombinant block B, with a cluster (>27%) occurring at a 12 kb region within the GTF2I/GTF2IP1 gene [31].
• A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK [10].
• Induction is inhibited by dominant interfering USF and TFII-I but not by the dominant negative I-kappaB protein [2].

Analytical, diagnostic and therapeutic context of GTF2I

• Chromatin immunoprecipitation analysis further reveals enhanced TFII-I binding to the Grp78 promoter in vivo upon ER stress [32].
• PATIENTS AND METHODS: Spin echo NMR images were obtained in 30 patients; 20 had chronic anemias treated by multiple blood transfusions, five had idiopathic hemochromatosis, and five had non-hemochromatotic liver disease with elevated serum ferritin levels and no stainable iron on liver biopsy [33].
• Lipid lateral phase separations. Spin label freeze-fracture electron microscopy studies [34].
• MATERIALS AND METHODS: Spin-echo and gradient-echo MR imaging was performed in 52 patients 1/2 to 200 months after composite graft replacement of the ascending aorta (22 for dissection, 30 for aneurysm) [35].
• Electrophoretic mobility shift assays demonstrated that the human MIS initiator sequence forms a specific DNA-protein complex with CH34 cell nuclear extract, HeLa cell nuclear extract, and purified TFII-I [36].

References