We
characterized the conformational preferences of DNA in an equimolar
mixture of complementary G-rich and C-rich strands from the promoter
region of the c-MYC oncogene. Our CD-based approach presupposes that
the CD spectrum of such a mixture is the spectral sum of the constituent
duplex, G-quadruplex, i-motif, and coiled conformations.
Spectra were acquired over a range of temperatures at different pHs
and concentrations of KCl. Each spectrum was unmixed in terms of the
predetermined spectra of the constituent conformational states to
obtain the corresponding weighting factors for their fractional contributions
to the total population of DNA. The temperature dependences of those
contributions then were analyzed in concert according to a model based
on a thermodynamic representation of the underlying equilibria. Fitted
estimates of the melting enthalpy and temperature obtained for the
duplex, G-quadruplex, and i-motif imply that the
driving force behind dissociation of the duplex and the concomitant
formation of tetrahelical structures is the folding of the G-strand
into the G-quadruplex. The liberated C-strand adopts the i-motif conformation at acidic pH and exists in the coiled state at
neutral pH. The i-motif alone cannot induce dissociation
of the duplex even at pH 5.0, at which it is most stable. Under the
physiological conditions of neutral pH, elevated potassium, and room
temperature, the duplex and G-quadruplex conformations coexist with
the C-strand in the coiled state. Taken together, our results suggest
a novel, thermodynamically controlled mechanism for the regulation
of gene expression.
It is now well established that the anionic porphyrin, N-methylmesoporphyrin IX (NMM) exhibits binding selectivity for the DNA G-quadruplex (G4) over other DNA secondary structures. Specifically, NMM binds, promotes and stabilizes a K þ -induced mixed-hybrid G4 conformation, and dem-
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