Subregions of the adenovirus E1A transactivation domain target multiple components of the TFIID complex.
Transcriptional activation by the adenovirus E1A 289R protein requires direct contacts with the TATA box-binding protein (TBP) and also displays a critical requirement for TBP-associated factors (TAFs) (T.G. Boyer and A. J. Berk, Genes Dev. 7:1810-1823, 1993; J. V. Geisberg, W. S. Lee, A. J. Berk, and R. P. Ricciardi, Proc. Natl. Acad. Sci. USA 91:2488-2492, 1994; W. S. Lee, C. C. Kao, G. O. Bryant, X. Liu, and A. J. Berk, Cell 67:365-376, 1991; and Q. Zhou, P. M. Lieberman, T. G. Boyer, and A. J. Berk, Genes Dev. 6:1964-1974, 1992). In this report, we demonstrate that the activation domain of E1A (CR3) specifically binds to two TAFs, human TAFII250 (hTAFII250) and Drosophila TAFII110 (dTAFII110). These interactions can take place both in vivo and in vitro and require the carboxy-terminal region of CR3; the zinc finger region of CR3, which binds TBP, is not needed to bind these TAFs. We mapped the E1A-binding sites on hTAFII250 to an internal region that contains a number of structural motifs, including an HMG box, a bromodomain, and direct repeats. This represents the first demonstration that hTAFII250 may serve as a target of a transcriptional activator. We also mapped the E1A binding on dTAFII110 to its C-terminal region. This is of significance since, by contrast, Sp1-mediated activation requires binding to the N-terminal domain of dTAFII110. Thus, distinct surfaces of dTAFII110 can serve as target sites for different activators. Our results indicate that E1A may activate transcription, in part, through direct contacts of the CR3 subdomains with selected components of the TFIID complex.
Geisberg
J V
JV
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Chen
J L
JL
Ricciardi
R P
RP
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D051548:Histone Acetyltransferases; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D016385:TATA Box; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators / Q000378:metabolism*; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016335:Zinc Fingers
D017500:Adenovirus E1A Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; C486319:TAF1C protein, human; D035381:TATA-Binding Protein Associated Factors; C103338:Taf4 protein, Drosophila; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa