Inhibitory effect of TIS7 on Sp1-C/EBPalpha transcription factor module activity.
The transcription factors C/EBPalpha and Sp1 functionally interact to induce expression of specific genes during myeloid and epithelial cell differentiation. The C/EBPalpha-Sp1 transcription factor "module" binds to enhancer elements within the upstream regulatory sequences of target genes. In our previous study we identified mouse TPA inducible sequence 7 (TIS7) as a novel co-repressor in epithelial cells undergoing loss of polarity. Increased levels of TIS7 down-regulate the transcription of a specific set of genes. Using bioinformatic analysis we identified a common binding site for the C/EBPalpha-Spl transcription factor module within the upstream regulatory regions of TIS7-regulated genes. The inhibitory effect of TIS7 on C/EBPalpha-Sp1-mediated transcription was confirmed by reporter assays. Our data showed that the TIS7 effect was mediated through specific interference with Sp1 transcriptional activity. Furthermore, TIS7 prevented formation of a complex between Sp1 protein and its consensus DNA binding site. Data presented here further specify the mechanism of action of the transcriptional co-repressor TIS7 as well as document the strength of a bioinformatic approach for the prediction and analysis of transcription factor modules.
Wick
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N
Clinical Institute for Pathology, University of Vienna, Austria Waehringer Guertel 18-20, A-1190 Vienna, Austria.
Schleiffer
A
A
Huber
L A
LA
Vietor
I
I
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D019295:Computational Biology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic
D022763:CCAAT-Enhancer-Binding Protein-alpha; C490045:IFRD1 protein, human; C490044:Ifrd1 protein, mouse; D017874:Immediate-Early Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor