Conformational Preferences Of Dna Strands From C-Myc Promoter Region

We report the first quantitative characterization of the conformational preferences of a system in which complementary G-rich and C-rich DNA strands exist in equimolar amounts mimicking the situation in the genome. We have employed a correlation analysis to deconvolute the CD spectra of the mixture of complementary G-rich and C-rich strands (from the promoter region of the c-MYC oncogene) in terms of the spectral sum of the duplex, G-quadruplex, i-motif, and coil conformations each with a weighting coefficient coinciding with the fractional population of the respective state. Our results are consistent with the picture in which the driving force behind duplex dissociation with the subsequent formation of tetraplex structures is the folding of the G-strand into G-quadruplex. The liberated C-strand adopts the i-motif conformation at acidic pH and remains in the coil state at neutral pH. We find that i-motif alone is not capable of inducing duplex dissociation even at pH 5.0 corresponding to the maximum of i-motif stability. At physiological conditions (neutral pH, elevated potassium concentrations, room temperature), the duplex and G-quadruplex conformations coexist with the C-strand being in the coil state. We discuss biological implications of our results.