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Abstract Abstract: To further explore the structure and function of the promoter and protein of human SIRT1 gene, our research used bioinformatic methods to analyze 5′-end promoter, promoter Motif, transcription factor binding sites, CpG island, single-nucleotide polymorphism, phylogenetic homology, physicochemical properties, hydrophilicity/hydrophobicity, secondary/tertiary structure, conserved domain, mutation site, N-glycosylation and phosphorylation sites, interacted proteins and biological function. The number of promoters predicted by TSSW and Neural Network Promoter Prediction database was 3 and 2 respectively. There were 3 Motifs found in the promoter region by using MEME database. The CpG islands were clustered in the 1 600~2 200 bp, which were found by using EMBOSS, MethPrimer and CpG Finder database. PROMO and AliBaba2.1 database showed that there were 22 transcription factors in their promoter regions. And there were 6 transcription factors found that bind to the positive and negative chains by using JASPAR software. Besides, there were differences found in allele frequencies between different ethnic groups by using SNP Function Prediction database. Human SIRT1 gene is located at chromosome 10q21.3 and widely distributed in different tissues, which is a hydrophilic and unstable protein with a high conservation among different species. The domain is located at the 254~489 amino acid sequence, belonging to the SIR2 superfamily, mainly located in the nucleus and mitochondria. The secondary structure of the protein mainly contains α-helices and irregular coiling. Compared with AlphaFold2, the tertiary structure model constructed by SWISS-MODEL database was reliable. SIRT1 contained 106 mutation sites, 1 N-glycosylation and 61 phosphorylation sites, which interacted with EP300, TP53 and other proteins. It also participated in circadian rhythm process, steroid hormone response, and intracellular receptor signaling etc., which were associated with longevity regulation pathway, AMPK signaling pathway, and FoxO signaling pathway etc. This study can provide a theoretical basis for further studying the effects on inflammatory reaction and other diseases of human SIRT1 gene.
Key words: human SIRT1 gene; promoter; protein; bioinformatics; inflammation
(Acta Laser Biology Sinica, 2023, 32(4): 368-384)
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