K+ promotes the favorable effect of polyamine on gene expression better than Na

PLoS One. 2020 Sep 3;15(9):e0238447. doi: 10.1371/journal.pone.0238447. eCollection 2020.

Abstract

Background: Polyamines are involved in a wide variety of biological processes including a marked effect on the structure and function of DNA. During our study on the interaction of polyamines with DNA, we found that K+ enhanced in vitro gene expression in the presence of polyamine more strongly than Na+. Thus, we sought to clarify the physico-chemical mechanism underlying this marked difference between the effects of K+ and Na+.

Principal findings: It was found that K+ enhanced gene expression in the presence of spermidine, SPD(3+), much more strongly than Na+, through in vitro experiments with a Luciferase assay on cell extracts. Single-DNA observation by fluorescence microscopy showed that Na+ prevents the folding transition of DNA into a compact state more strongly than K+. 1H NMR measurement revealed that Na+ inhibits the binding of SPD to DNA more strongly than K+. Thus, SPD binds to DNA more favorably in K+-rich medium than in Na+-rich medium, which leads to favorable conditions for RNA polymerase to access DNA by decreasing the negative charge.

Conclusion and significance: We found that Na+ and K+ exhibit markedly different effects through competitive binding with a cationic polyamine, SPD, to DNA, which causes a large difference in the higher-order structure of genomic DNA. It is concluded that the larger favorable effect of Na+ than K+ on in vitro gene expression observed in this study is well attributable to the significant difference between Na+ and K+ on the competitive binding inducing conformational transition of DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biochemical Phenomena
  • DNA / metabolism
  • Gene Expression / drug effects*
  • Polyamines / metabolism
  • Polyamines / pharmacology
  • Potassium / metabolism*
  • Sodium / metabolism*
  • Spermidine / pharmacology
  • Spermine / pharmacology

Substances

  • Polyamines
  • Spermine
  • DNA
  • Sodium
  • Potassium
  • Spermidine

Grants and funding

This work was supported by JSPS KAKENHI Grant Number JP15H02121 and JP20H01877 funded to KY. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.