Prediction of the affinity of the TATA-binding protein to TATA boxes with single nucleotide polymorphisms

Abstract

The TATA-binding protein (TBP) is the subunit of basal transcription factor TFIID that recognizes the TATA boxes of TATA-containing promoters in class II genes, binds to them, and starts the assemblage of the RNA polymerase II basal transcription complex. The sequence of the TATA box with its flanking regions affects the levels of basal and activated transcription. The association of polymorphic TATA boxes with human hereditary diseases supports the hypothesis that TBP-TATA interaction modulates gene expression in vivo. The objective of this work is to determine changes in the TBP/TATA affinity related to polymorphisms in TATA boxes of human promoters. Changes in TBP/TATA affinities were assessed in silico by using our equation for equilibrium TBP/TATA binding in four consecutive steps: nonspecific binding ↔ sliding ↔ braking (stopping) ↔ stabilization. Our predictions agree with known examples of TATA-box polymorphisms and human hereditary diseases associated with them.