Identification of the relationship between the variability of the expression of signaling pathway genes in the human brain and the affinity of TATA-binding protein to their promoters

Abstract

Variations in gene expression are the subject of a wide range of research aimed at the reconstruction of regulatory protein binding sites on DNA, regulatory gene regions, gene networks, signaling pathways, and many other entities that are able to modify gene expression. Pearson’s coefficient of variation (Cv, the ratio of the standard deviation to the mean) is the measure of variations in gene expression that is the most used in the fields of intense biomedical and breeding research. In turn, only one common genomic regulatory signal has been identified in all eukaryotes, namely, the TATA box, together with three other, less conservative, obligatory elements of core promoters accompanying it: DPE, BPE, and INR. We applied the equation for TATA box Binding Protein (TBP) affinity to TATA boxes deduced from our experimental data to the analysis of high-throughput sequencing data on 35609 mRNAs in 946 human brain segments taken from the Allen Brain Atlas. The analysis revealed a significant correlation between the affinity of TBP binding to promoters of signaling pathways genes and in silico estimates of Pearson’s Cv of the expression of these genes. This finding may help scientists analyze high-throughput sequencing data in order to identify more candidate factors modifying gene expression.