Inhibitory Effect of TIS7 on Sp1-C/EBPα Transcription Factor Module Activity

The transcription factors C/EBPα and Sp1 functionally interact to induce expression of specific genes during myeloid and epithelial cell differentiation. The C/EBPα-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/EBPα-Sp1 transcription factor module within the upstream regulatory regions of TIS7-regulated genes. The inhibitory effect of TIS7 on C/EBPα-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.