A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the dTAFII110 component of the Drosophila TFIID complex and mediates transcriptional activation.
Activation of transcription by the promoter-specific factor Sp1 requires coactivators that are tightly associated with the TATA-box-binding protein (TBP) in the TFIID complex. Recent work has shown that the two glutamine-rich activation domains of Sp1, A and B, can interact with at least one component of this complex, the TBP-associated factor dTAFII110. Here we report the mapping of a region of Sp1 with alternating glutamine and hydrophobic residues which is required for the interaction with dTAFII110 and is important for mediating transcriptional activation. Substitution of bulky hydrophobic residues within this region decreased both interaction with dTAFII110 and transcriptional activation in Drosophila cells. In contrast, mutation of glutamine residues in this region had no effect. Thus, the strength of the Sp1-TAF interaction correlates with the potency of Sp1 as a transcriptional activator, indicating that this activator-TAF interaction is an important part of the mechanism of transcriptional activation. Sequence comparison of three activation domains shown to bind dTAFII110 suggests that different activators that utilize dTAFII110 as a coactivator may share common sequence features that we have determined to be important for the Sp1-dTAFII110 interaction.
Gill
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Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Pascal
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E
Tseng
Z H
ZH
Tjian
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R
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004331:Drosophila melanogaster; D005973:Glutamine / Q000737:chemistry; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D046911:Macromolecular Substances; D016329:Sp1 Transcription Factor; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D005973:Glutamine