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

Abstract

BackgroundBiologists 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.ResultsThis 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.ConclusionsThis 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.

Control of organelle gene expression by the mitochondrial transcription termination factor mTERF22 in Arabidopsis thaliana plants

“…The RNA profiles and run-on experiments may indicate to functional redundancy, where various transcription factors are compensating for one another (see e.g., [ 91 ]). Based on phylogenetic analyses of the mTERF family in plants ( S8A Fig and [ 28 , 29 , 46 ]), mTERF7 (At5g07900) and mTERF27 (At1g21150) are closely related to mTERF22.…”

Differential regulation of cryptic genetic variation shapes the genetic interactome underlying complex traits

“…However, the mainly additive nature of causal genetic variation in mapping studies challenges the role of loci regulating CGV in phenotypic variation. At a molecular level, high genetic crosstalk resulting in redundant pathways (Wu and Lai 2015) has been proposed to be a compensatory mechanism to buffer CGV (Costanzo et al 2010) indicating its pervasive role in shaping the genetic architecture. Therefore, in order to understand the impact of CGV on phenotypic variation, it is important to study its regulation at a genome-wide level.…”

Transcriptional engineering of the glyceraldehyde‐3‐phosphate dehydrogenase promoter for improved heterologous protein production in Pichia pastoris

“…One possible explanation for this is the compensation of Rfx1 by other factors; therefore, eliminating just one transcription factor may not be enough to observe a significant difference. This speaks for a high functional redundancy of the transcriptional control (Wu and Lai, ).…”