Effects of Structural Isomers of Spermine on the Higher-Order Structure of DNA and Gene Expression

• Published in: International journal of molecular sciences Vol. 22; no. 5; p. 2355
• Main Authors: Kitagawa, Tomoki, Nishio, Takashi, Yoshikawa, Yuko, Umezawa, Naoki, Higuchi, Tsunehiko, Shew, Chwen-Yang, Kenmotsu, Takahiro, Yoshikawa, Kenichi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2021; MDPI
• Subjects: Amino groups; Atomic force microscopy; Bacteriophage T4 - chemistry; Bacteriophage T4 - genetics; Bacteriophage T4 - metabolism; bimodal effect of promotion and inhibition; Cell differentiation; Cell proliferation; Conformation; Deoxyribonucleic acid; DNA; DNA structure; DNA, Viral - chemistry; DNA, Viral - genetics; DNA, Viral - metabolism; Evaluation; Fluorescence; Fluorescence microscopy; Gene expression; Gene Expression Regulation, Viral; Gene regulation; higher-order structure of DNA; Isomerism; Isomers; Microscopy; Models, Molecular; Nucleic Acid Conformation; Organisms; polyamine; Polyamines; Spermine; Spermine - analogs & derivatives; Spermine - chemistry; Spermine - metabolism; polyamine; higher-order structure of DNA; bimodal effect of promotion and inhibition; gene expression
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22052355

Polyamines are involved in various biological functions, including cell proliferation, differentiation, gene regulation, etc. Recently, it was found that polyamines exhibit biphasic effects on gene expression: promotion and inhibition at low and high concentrations, respectively. Here, we compared the effects of three naturally occurring tetravalent polyamines, spermine (SPM), thermospermine (TSPM), and -aminopropylspermidine (BSPD). Based on the single DNA observation with fluorescence microscopy together with measurements by atomic force microscopy revealed that these polyamines induce shrinkage and then compaction of DNA molecules, at low and high concentrations, respectively. We also performed the observation to evaluate the effects of these polyamine isomers on the activity of gene expression by adapting a cell-free luciferase assay. Interestingly, the potency of their effects on the DNA conformation and also on the inhibition of gene expression activity indicates the highest for TSPM among spermine isomers. A numerical evaluation of the strength of the interaction of these polyamines with negatively charged double-strand DNA revealed that this ordering of the potency corresponds to the order of the strength of the attractive interaction between phosphate groups of DNA and positively charged amino groups of the polyamines.