Human_SNP_TATAdb: a database of SNPs that statistically significantly change the affinity of the TATA-binding protein to human gene promoters: genome-wide analysis and use cases

Abstract

It was previously shown that the expression levels of human genes positively correlate with TBP affinity for the promoters of these genes. In turn, single nucleotide polymorphisms (SNPs) in human gene promoters can affect TBP affinity for DNA and, as a consequence, gene expression. The Institute of Cytology and Genetics SB RAS (ICG) has developed a method for predicting TBP affinity for gene promoters based on a three-step binding mechanism: (1) TBP slides along DNA, (2) TBP stops at the binding site, and (3) the TBP-promoter complex is fixed due to DNA helix bending. The method showed a high correlation of theoretical predictions with measured values during repeated experimental testing by independent groups of researchers. This model served as a base for other ICG web services, SNP_TATA_Z-tester and SNP_TATA_Comparator, which make a statistical assessment of the SNP-induced change in the affinity of TBP binding to the human gene promoter and help predict changes in expression that may be associated with a genetic predisposition to diseases or phenotypic features of the organism. In this work, we integrated into a single database information about SNPs in human gene promoters obtained by automatic extraction from various heterogeneous data sources, as well as the estimates of TBP affinity for the promoter obtained using the three-step binding model and predicting their effect on gene expression for wild-type promoters and promoters with SNPs. We have shown that Human_SNP_TATAdb can be used for annotation and identification of candidate SNP markers of diseases. The results of a genome-wide data analysis are presented, including the distribution of genes with respect to the number of transcripts, the distribution of SNPs affecting TBP-DNA affinity with respect to positions within promoters, as well as patterns linking TBP affinity for the promoter, the specificity of the TBP binding site for the promoter and other characteristics of promoters. The results of the genome-wide analysis showed that the affinity of TBP for the promoter and the specificity of its binding site are statistically related to other characteristics of promoters important for the functional classification of promoters and the study of the features of differential gene expression.