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Gene Review

GTF2I  -  general transcription factor IIi

Homo sapiens

Synonyms: BAP-135, BAP135, BTK-associated protein 135, BTKAP1, Bruton tyrosine kinase-associated protein 135, ...
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Disease relevance of GTF2I


Psychiatry related information on GTF2I


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


Associations of GTF2I with chemical compounds


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


  1. Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Hirota, H., Matsuoka, R., Chen, X.N., Salandanan, L.S., Lincoln, A., Rose, F.E., Sunahara, M., Osawa, M., Bellugi, U., Korenberg, J.R. Genet. Med. (2003) [Pubmed]
  2. TFII-I regulates induction of chromosomally integrated human immunodeficiency virus type 1 long terminal repeat in cooperation with USF. Chen, J., Malcolm, T., Estable, M.C., Roeder, R.G., Sadowski, I. J. Virol. (2005) [Pubmed]
  3. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF. Roy, A.L., Meisterernst, M., Pognonec, P., Roeder, R.G. Nature (1991) [Pubmed]
  4. A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes. Hakimi, M.A., Dong, Y., Lane, W.S., Speicher, D.W., Shiekhattar, R. J. Biol. Chem. (2003) [Pubmed]
  5. GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region. Morris, C.A., Mervis, C.B., Hobart, H.H., Gregg, R.G., Bertrand, J., Ensing, G.J., Sommer, A., Moore, C.A., Hopkin, R.J., Spallone, P.A., Keating, M.T., Osborne, L., Kimberley, K.W., Stock, A.D. Am. J. Med. Genet. A (2003) [Pubmed]
  6. Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Roy, A.L., Carruthers, C., Gutjahr, T., Roeder, R.G. Nature (1993) [Pubmed]
  7. An alternative pathway for transcription initiation involving TFII-I. Roy, A.L., Malik, S., Meisterernst, M., Roeder, R.G. Nature (1993) [Pubmed]
  8. Opposing Functions of TFII-I Spliced Isoforms in Growth Factor-Induced Gene Expression. Hakre, S., Tussie-Luna, M.I., Ashworth, T., Novina, C.D., Settleman, J., Sharp, P.A., Roy, A.L. Mol. Cell (2006) [Pubmed]
  9. DNA-binding properties and characterization of human transcription factor TFIIIC2. Boulanger, P.A., Yoshinaga, S.K., Berk, A.J. J. Biol. Chem. (1987) [Pubmed]
  10. 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. Pérez Jurado, L.A., Wang, Y.K., Peoples, R., Coloma, A., Cruces, J., Francke, U. Hum. Mol. Genet. (1998) [Pubmed]
  11. JAK2 activates TFII-I and regulates its interaction with extracellular signal-regulated kinase. Kim, D.W., Cochran, B.H. Mol. Cell. Biol. (2001) [Pubmed]
  12. Identification of a novel slow-muscle-fiber enhancer binding protein, MusTRD1. O'Mahoney, J.V., Guven, K.L., Lin, J., Joya, J.E., Robinson, C.S., Wade, R.P., Hardeman, E.C. Mol. Cell. Biol. (1998) [Pubmed]
  13. Regulation of alternative splicing of Gtf2ird1 and its impact on slow muscle promoter activity. Tay, E.S., Guven, K.L., Subramaniam, N., Polly, P., Issa, L.L., Gunning, P.W., Hardeman, E.C. Biochem. J. (2003) [Pubmed]
  14. Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6. Parker, R., Phan, T., Baumeister, P., Roy, B., Cheriyath, V., Roy, A.L., Lee, A.S. Mol. Cell. Biol. (2001) [Pubmed]
  15. Antagonistic regulation of beta-globin gene expression by helix-loop-helix proteins USF and TFII-I. Crusselle-Davis, V.J., Vieira, K.F., Zhou, Z., Anantharaman, A., Bungert, J. Mol. Cell. Biol. (2006) [Pubmed]
  16. Identification of phosphorylation sites for Bruton's tyrosine kinase within the transcriptional regulator BAP/TFII-I. Egloff, A.M., Desiderio, S. J. Biol. Chem. (2001) [Pubmed]
  17. The Rous sarcoma virus long terminal repeat promoter is regulated by TFII-I. Mobley, C.M., Sealy, L. J. Virol. (2000) [Pubmed]
  18. Human SWI-SNF component BRG1 represses transcription of the c-fos gene. Murphy, D.J., Hardy, S., Engel, D.A. Mol. Cell. Biol. (1999) [Pubmed]
  19. Regulation of TFII-I activity by phosphorylation. Novina, C.D., Cheriyath, V., Roy, A.L. J. Biol. Chem. (1998) [Pubmed]
  20. Identification of the interface between cGMP-dependent protein kinase Ibeta and its interaction partners TFII-I and IRAG reveals a common interaction motif. Casteel, D.E., Boss, G.R., Pilz, R.B. J. Biol. Chem. (2005) [Pubmed]
  21. Nematic ordering of suspension of charged anisotropic colloids detected by multinuclear quadrupolar spectra and ( 1)H PGSE-NMR measurements. Porion, P., Al-Mukhtar, M., Faugère, A.M., Meyer, S., Delville, A. The European physical journal. E, Soft matter. (2003) [Pubmed]
  22. Vascular endothelial growth factor receptor-2: counter-regulation by the transcription factors, TFII-I and TFII-IRD1. Jackson, T.A., Taylor, H.E., Sharma, D., Desiderio, S., Danoff, S.K. J. Biol. Chem. (2005) [Pubmed]
  23. Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I. Wen, Y.D., Cress, W.D., Roy, A.L., Seto, E. J. Biol. Chem. (2003) [Pubmed]
  24. Identification of human TFIID components and direct interaction between a 250-kDa polypeptide and the TATA box-binding protein (TFIID tau). Takada, R., Nakatani, Y., Hoffmann, A., Kokubo, T., Hasegawa, S., Roeder, R.G., Horikoshi, M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  25. NF-kappa B homodimer binding within the HIV-1 initiator region and interactions with TFII-I. Montano, M.A., Kripke, K., Norina, C.D., Achacoso, P., Herzenberg, L.A., Roy, A.L., Nolan, G.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  26. Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase. Novina, C.D., Kumar, S., Bajpai, U., Cheriyath, V., Zhang, K., Pillai, S., Wortis, H.H., Roy, A.L. Mol. Cell. Biol. (1999) [Pubmed]
  27. Action of TFII-I outside the nucleus as an inhibitor of agonist-induced calcium entry. Caraveo, G., van Rossum, D.B., Patterson, R.L., Snyder, S.H., Desiderio, S. Science (2006) [Pubmed]
  28. 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. Stasyk, T., Dubrovska, A., Lomnytska, M., Yakymovych, I., Wernstedt, C., Heldin, C.H., Hellman, U., Souchelnytskyi, S. Mol. Biol. Cell (2005) [Pubmed]
  29. TFII is required for transcription of the naturally TATA-less but initiator-containing Vbeta promoter. Manzano-Winkler, B., Novina, C.D., Roy, A.L. J. Biol. Chem. (1996) [Pubmed]
  30. GTF2IRD2 is located in the Williams-Beuren syndrome critical region 7q11.23 and encodes a protein with two TFII-I-like helix-loop-helix repeats. Makeyev, A.V., Erdenechimeg, L., Mungunsukh, O., Roth, J.J., Enkhmandakh, B., Ruddle, F.H., Bayarsaihan, D. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  31. Mutational mechanisms of Williams-Beuren syndrome deletions. Bayés, M., Magano, L.F., Rivera, N., Flores, R., Pérez Jurado, L.A. Am. J. Hum. Genet. (2003) [Pubmed]
  32. Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation. Hong, M., Lin, M.Y., Huang, J.M., Baumeister, P., Hakre, S., Roy, A.L., Lee, A.S. J. Biol. Chem. (2005) [Pubmed]
  33. Assessment of tissue iron overload by nuclear magnetic resonance imaging. Johnston, D.L., Rice, L., Vick, G.W., Hedrick, T.D., Rokey, R. Am. J. Med. (1989) [Pubmed]
  34. Lipid lateral phase separations. Spin label freeze-fracture electron microscopy studies. Grant, C.W. Biophys. J. (1975) [Pubmed]
  35. Composite graft replacement of the ascending aorta: leakage detection with gadolinium-enhanced MR imaging. Fattori, R., Descovich, B., Bertaccini, P., Celletti, F., Caldarera, I., Pierangeli, A., Gavelli, G. Radiology. (1999) [Pubmed]
  36. Human Müllerian-inhibiting substance promoter contains a functional TFII-I-binding initiator. Morikawa, N., Clarke, T.R., Novina, C.D., Watanabe, K., Haqq, C., Weiss, M., Roy, A.L., Donahoe, P.K. Biol. Reprod. (2000) [Pubmed]
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