Effects of SNPs in the positioning regions of RNA polymerase II on the TBP/promoter affinity in genes of the human circadian clock

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• 作者：O. A. Podkolodnaya ; D. A. Rasskazov…
• 关键词：circadian rhythm ; promoter ; SNP ; TATAbinding protein (TBP) ; affinity of TBP promoter ; gene expression
• 刊名：Russian Journal of Genetics: Applied Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：6
• 期：7
• 页码：759-770
• 全文大小：197 KB
• 刊物主题：Human Genetics;
• 出版者：Springer US
• ISSN：2079-0600
• 卷排序：6

文摘

Genetic variability in genes of the circadian clock can manifest itself as a phenotypic variability of physiological functions and behavior, as well as functional disorders not only of the clock but also of other systems leading to the development of pathologies. We analyzed the influence of SNPs localized in the [–70,–20] region from the transcription start site on the promoter affinity of the TATA-binding protein (TBP) in two groups of genes that are components of the human circadian clock system. The first group is comprised of the genes of the core of the circadian oscillator (11 genes); the second comprises the genes of nearest regulatory environment of the circadian oscillator components (21 genes).The control comparison group included genes with other functions (31 genes). The SNP_TATA_Comparator web service was used to predict the effects of the SNPs in the regions of the RNA polymerase II positioning on the TBP/promoter dissociation constant. It was shown that the number of SNP markers reducing the TBP/promoter affinity in the first group of genes is significantly lower than the number of SNP markers increasing affinity (α < 10–3). The opposite was true for the comparison group. A significantly greater number of SNP markers reduced the TBP/promoter affinity than increased it (α < 10–6). Thus, this property may represent a characteristic feature of the genes of the circadian oscillator that may ensure its stability during the genetic variability of the analyzed promoter regions. These predictions are important for identifying the candidate SNP markers for various pathologies associated with the dysfunction of the circadian clock genes for further testing in the experimental and clinical studies, as well as for the verification of the mathematical models of the circadian oscillator.