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Gene Review

GTF2A1  -  general transcription factor IIA, 1, 19/37kDa

Homo sapiens

Synonyms: General transcription factor IIA subunit 1, TF2A1, TFIIA, TFIIA-42, TFIIAL, ...
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Disease relevance of GTF2A1


High impact information on GTF2A1

  • Transcription from linear DNA templates containing either the IgH or the adenovirus major late promoters (MLPs) requires in addition TFIIF, TFIIE, TFIIH, and a fraction containing TFIIA and TFIIJ [6].
  • A family of proteins was shown to bind cooperatively with TFIID to core promoters, as previously demonstrated for the general initiation factor TFIIA [7].
  • Recombinant TFIID forms a stable complex on a TATA box either alone or in combination with either of the general transcription factors, TFIIA or TFIIB [8].
  • In DNase I footprinting assays, GAL4-VP16 recruited TFIID-TFIIA to core promoters containing either a TATA box, an Inr, or both TATA and Inr elements, with synergistic interactions apparent on the TATA-Inr promoter [9].
  • Recombinant TFIIA functioned in transcriptional activation whether expressed as a dimer (alpha beta+gamma) or as a trimer (alpha+beta+gamma), which closely resembles the native form [10].

Biological context of GTF2A1

  • Previously, we have found that phosphorylation of yeast TFIIA stimulates TFIIA.TBP.TATA complex formation and transcription activation in vivo [2].
  • However, phosphorylation of TFIIA containing a gamma subunit Y65A mutation strongly stimulated TFIIA.TBP.TATA complex formation [2].
  • TFIIA cross-linked to the coding strand opposite TBP at the TATA box and cross-linked upstream of TBP around position -40 [11].
  • Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function [2].
  • This protein-protein interaction on promoter DNA minimally requires the presence of one GAL4 binding site and the formation of a quaternary complex containing TBP, TFIIB, and TFIIA on the TATA element [12].

Anatomical context of GTF2A1

  • By use of a mobility shift assay, TFIIA was purified from HeLa cells as a complex of 35-, 19-, and 12-kD subunits [1].
  • The TFIIA-related protein (TFIIAtau) was cloned from a testis-specific cDNA library, and its mRNA is expressed predominantly in testis tissue as determined by expressed sequence tag data base analysis and Northern blotting analysis [13].
  • The addition of either highly purified human or recombinant yeast transcription factor IIA (TFIIA) to extracts from mature erythrocytes resulted in a significant increase in transcription from TATA-containing promoters, whereas transcription from TATA-less promoters remained unaffected [14].
  • Third, a coimmunoprecipitation assay showed that in HTLV-1-infected human T lymphocytes, Tax and TFIIA were associated [15].
  • Steady-state protein levels of the TFIIA tau, alphabeta, and gamma subunits were significantly reduced when human embryonal (ec) and hepatic carcinoma cell lines were stimulated to differentiate with either all-trans-retinoic acid (ATRA) or sodium butyrate [16].

Associations of GTF2A1 with chemical compounds

  • We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits [2].
  • Agarose gel electrophoretic mobility shift showed that a preformed Zta-holo-TFIID-TFIIA complex was resistant to Sarkosyl and to Zta response element oligonucleotide challenge [17].
  • Formaldehyde cross-linking revealed that in EC but not in differentiated cells, association of TBP with chromatin is strongly enhanced when complexed with TFIIA in vivo [4].
  • Interestingly, acetyl-CoA also caused a conformational change in the TFIID-TFIIA-promoter complex as assessed by DNase I footprinting [18].

Physical interactions of GTF2A1

  • These results provide functional and physical evidence that the Zta transcriptional activator influences at least two distinct steps in preinitiation complex assembly, the formation of the stable holo-TFIID-TFIIA-promoter complex and the subsequent binding of TFIIB and a USA-like coactivator [17].
  • In addition, N-terminal truncation of the TFIID point mutants defective for DNA binding mimicked the ability of TFIIA to restore DNA binding of those mutants [19].

Enzymatic interactions of GTF2A1


Other interactions of GTF2A1


Analytical, diagnostic and therapeutic context of GTF2A1

  • Molecular cloning of the small (gamma) subunit of human TFIIA reveals functions critical for activated transcription [10].
  • TFIIA was found to interact with the TBP and was extensively purified by the use of affinity chromatography on columns containing immobilized recombinant yeast TBP [24].
  • In addition, DNA immunoprecipitation experiments indicate that T antigen is associated with the stabilized TBP-TFIIA complexes bound to the DNA [25].
  • The transcription factor TFIIA stabilizes the interaction between the TATA-binding protein (TBP) and promoter DNA and facilitates activator function [26].
  • The dispensability of TFIIA for ICP4 activation of the gC promoter required an intact INR element [27].


  1. A single cDNA, hTFIIA/alpha, encodes both the p35 and p19 subunits of human TFIIA. DeJong, J., Roeder, R.G. Genes Dev. (1993) [Pubmed]
  2. Taf(II) 250 phosphorylates human transcription factor IIA on serine residues important for TBP binding and transcription activity. Solow, S., Salunek, M., Ryan, R., Lieberman, P.M. J. Biol. Chem. (2001) [Pubmed]
  3. Assembly of the isomerized TFIIA--TFIID--TATA ternary complex is necessary and sufficient for gene activation. Chi, T., Carey, M. Genes Dev. (1996) [Pubmed]
  4. TAC, a TBP-sans-TAFs complex containing the unprocessed TFIIAalphabeta precursor and the TFIIAgamma subunit. Mitsiou, D.J., Stunnenberg, H.G. Mol. Cell (2000) [Pubmed]
  5. Second-site long terminal repeat (LTR) revertants of replication-defective human immunodeficiency virus: effects of revertant TATA box motifs on virus infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of basal transcription factors TFIID and TFIIA. Kashanchi, F., Shibata, R., Ross, E.K., Brady, J.N., Martin, M.A. J. Virol. (1994) [Pubmed]
  6. DNA topology and a minimal set of basal factors for transcription by RNA polymerase II. Parvin, J.D., Sharp, P.A. Cell (1993) [Pubmed]
  7. Family of proteins that interact with TFIID and regulate promoter activity. Meisterernst, M., Roeder, R.G. Cell (1991) [Pubmed]
  8. Functional domains and upstream activation properties of cloned human TATA binding protein. Peterson, M.G., Tanese, N., Pugh, B.F., Tjian, R. Science (1990) [Pubmed]
  9. Mechanism of synergy between TATA and initiator: synergistic binding of TFIID following a putative TFIIA-induced isomerization. Emami, K.H., Jain, A., Smale, S.T. Genes Dev. (1997) [Pubmed]
  10. Molecular cloning of the small (gamma) subunit of human TFIIA reveals functions critical for activated transcription. Ozer, J., Moore, P.A., Bolden, A.H., Lee, A., Rosen, C.A., Lieberman, P.M. Genes Dev. (1994) [Pubmed]
  11. Topological localization of the human transcription factors IIA, IIB, TATA box-binding protein, and RNA polymerase II-associated protein 30 on a class II promoter. Coulombe, B., Li, J., Greenblatt, J. J. Biol. Chem. (1994) [Pubmed]
  12. Interactions of a DNA-bound transcriptional activator with the TBP-TFIIA-TFIIB-promoter quaternary complex. Dion, V., Coulombe, B. J. Biol. Chem. (2003) [Pubmed]
  13. A testis-specific transcription factor IIA (TFIIAtau) stimulates TATA-binding protein-DNA binding and transcription activation. Ozer, J., Moore, P.A., Lieberman, P.M. J. Biol. Chem. (2000) [Pubmed]
  14. Transcription factor IIA is inactivated during terminal differentiation of avian erythroid cells. Bungert, J., Waldschmidt, R., Kober, I., Seifart, K.H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  15. Interaction of the human T-cell lymphotropic virus type 1 tax transactivator with transcription factor IIA. Clemens, K.E., Piras, G., Radonovich, M.F., Choi, K.S., Duvall, J.F., DeJong, J., Roeder, R., Brady, J.N. Mol. Cell. Biol. (1996) [Pubmed]
  16. Transcription Factor IIA tau Is Associated with Undifferentiated Cells and Its Gene Expression Is Repressed in Primary Neurons at the Chromatin Level In Vivo. Howe, M.L., Mehmud, Z.F., Saha, S., Buratovich, M., Stutius, E.A., Schmidt, H.D., Lenon, A.L., Reddicks, C., Ivanov, G.S., Przyborski, S.A., Ozer, J.S. Stem Cells Dev. (2006) [Pubmed]
  17. Identification of functional targets of the Zta transcriptional activator by formation of stable preinitiation complex intermediates. Lieberman, P. Mol. Cell. Biol. (1994) [Pubmed]
  18. Acetyl coenzyme A stimulates RNA polymerase II transcription and promoter binding by transcription factor IID in the absence of histones. Galasinski, S.K., Lively, T.N., Grebe De Barron, A., Goodrich, J.A. Mol. Cell. Biol. (2000) [Pubmed]
  19. TFIIA induces conformational changes in TFIID via interactions with the basic repeat. Lee, D.K., DeJong, J., Hashimoto, S., Horikoshi, M., Roeder, R.G. Mol. Cell. Biol. (1992) [Pubmed]
  20. Uncleaved TFIIA is a substrate for taspase 1 and active in transcription. Zhou, H., Spicuglia, S., Hsieh, J.J., Mitsiou, D.J., Høiby, T., Veenstra, G.J., Korsmeyer, S.J., Stunnenberg, H.G. Mol. Cell. Biol. (2006) [Pubmed]
  21. Corepressor required for adenovirus E1B 55,000-molecular-weight protein repression of basal transcription. Martin, M.E., Berk, A.J. Mol. Cell. Biol. (1999) [Pubmed]
  22. Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor. Na, S.Y., Choi, H.S., Kim, J.W., Na, D.S., Lee, J.W. J. Biol. Chem. (1998) [Pubmed]
  23. TFIIA plays a role in the response to oxidative stress. Kraemer, S.M., Goldstrohm, D.A., Berger, A., Hankey, S., Rovinsky, S.A., Scott Moye-Rowley, W., Stargell, L.A. Eukaryotic Cell (2006) [Pubmed]
  24. Factors involved in specific transcription by mammalian RNA polymerase II: purification and analysis of transcription factor IIA and identification of transcription factor IIJ. Cortes, P., Flores, O., Reinberg, D. Mol. Cell. Biol. (1992) [Pubmed]
  25. Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. Damania, B., Lieberman, P., Alwine, J.C. Mol. Cell. Biol. (1998) [Pubmed]
  26. Expression of human TFIIA subunits in Saccharomyces cerevisiae identifies regions with conserved and species-specific functions. Upadhyaya, A.B., DeJong, J. Biochim. Biophys. Acta (2003) [Pubmed]
  27. Differential cellular requirements for activation of herpes simplex virus type 1 early (tk) and late (gC) promoters by ICP4. Zabierowski, S., DeLuca, N.A. J. Virol. (2004) [Pubmed]
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