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Background: transcription factors (TFs) bind at the specific DNA sequences and interact with components of the polymerase complexes to initiate the eukaryotic transcription in a combinatorial way.A complete TF network containing 762 human interactions has been mapped using the mammalian two-hybrid system.Methods: we investigated the expression of genes regulated by the interactive TFs in the study.Activators and repressors are considered as the TFs that positively and negatively regulate the transcription respectively.We also analyzed the expression of genes regulated by the activators and repressors, which were based on the annotation of UniProt databases.The binding sites of 164 TFs were inferred with algorithm CENTIPEDE and the target genes regulated by specific TFs were considered as the genes that contained the TF binding sites in the 5000 bp promoter.The expression data of all RefSeq genes were divided into four equal groups and the genes within the highest (lowest) group were considered as genes with high (low) expression.Results: for genes regulated by activators only and repressors only, the percent of genes with high expression was 31.8% and 24.5% respectively, while the percent of genes with low expression was 13.0% and 19.8% respectively, indicating that the existence of activator binding was not sufficient to activate the transcription and the repressors ineffectively inhibited the transcription.However, the genes containing the interactive TF binding sites and genes regulated by both activators and repressors showed higher expression, suggesting that the combinatorial binding might the determinant of transcriptional level.Besides, we investigated the distance between the binding sites of the interactive TFs.47.3% interactive sites showed a distance of less than 50 bp, suggesting that most TFs closely clustered together to regulate the gene expression.Conclusions: the transcriptional output of a gene is due to the joint activity of many TFs which function interdependently and the analysis of TF combinatorial binding would help to understand the spatio-temporal patterns of gene expression .