Functional redundancy of transcription factors explains why most binding targets of a transcription factor are not affected when the transcription factor is knocked out

Background: Biologists are puzzled by the extremely low percentage (3%) of the binding targets of a yeast transcription factor (TF) affected when the TF is knocked out, a phenomenon observed by comparing the TF binding dataset and TF knockout effect dataset. Results: This study gives a plausible biological explanation of this counterintuitive phenomenon. Our analyses find that TFs with high functional redundancy show significantly lower percentage than do TFs with low functional redundancy. This suggests that functional redundancy may lead to one TF compensating for another, thus masking the TF knockout effect on the binding targets of the knocked-out TF. In addition, we show that seven classes of genes (lowly expressed genes, TATA box-less genes, genes containing a nucleosome-free region immediately upstream of the transcriptional start site (TSS), genes with low transcriptional plasticity, genes with a low number of bound TFs, genes with a low number of TFBSs, and genes with a short average distance of TFBSs to the TSS) are insensitive to the knockout of their promoter-binding TFs, providing clues for finding other biological explanations of the surprisingly low percentage of the binding targets of a TF affected when the TF is knocked out. Conclusions: This study shows that one property of TFs (functional redundancy) and seven properties of genes (expression level, TATA box, nucleosome, transcriptional plasticity, the number of bound TFs, the number of TFBSs, and the average distance of TFBSs to the TSS) may be useful for explaining a counterintuitive phenomenon: most binding targets of a yeast transcription factor are not affected when the transcription factor is knocked out.