Ability of spermine to differentiate between DNA sequences—Preferential stabilization of A-tracts Original Research Article

The regulatory roles fulfilled by polyamines by governance of chromatin structure are made possible by their strong association with cellular DNA, and hence by their ability to modulate DNA structure and function. Towards this end, it is crucial to understand the manifestation of sequence-dependent polyamine binding at the secondary and tertiary structural levels of DNA. This study utilizes circular dichroism (CD) and isothermal titration calorimetry (ITC) to address this relationship by using 20 bp oligonucleotides with sequences–poly(dA):poly(dT), poly(dAdT):poly(dAdT), poly(dG):poly(dC), poly(dGdC):poly(dGdC)–that yield physiologically relevant structures, and poly(dIdC):poly(dIdC). CD studies show that at physiological ionic strength (150 mM NaCl), spermine preferentially stabilizes A-tracts, and increases flexibility of the G-tract oligomer; the latter is also suggested by the larger change in entropy (ΔS) of spermine binding to G-tracts. Given the chromatin destabilizing property of these sequences, these findings suggest a role for spermine in stabilization of non-nucleosomal A-tracts, and a compensating mechanism for incorporation of G-tracts in the chromatin structure. Other implications of these findings in sequence dependent DNA packaging are discussed.