I-motif structures formed in the human c-MYC promoter are highly dynamic--insights into sequence redundancy and I-motif stability.
The GC-rich nuclease hypersensitivity element III1 (NHE III1) of the c-MYC promoter largely controls the transcriptional activity of the c-MYC oncogene. The C-rich strand in this region can form I-motif DNA secondary structures. We determined the folding pattern of the major I-motif formed in the NHE III1, which can be formed at near-neutral pH. While we find that the I-motif formed in the four 3' consecutive runs of cytosines appears to be the most favored, our results demonstrate that the C-rich strand of the c-MYC NHE III1 exhibits a high degree of dynamic equilibration. Using a trisubstituted oligomer of this region, we determined the formation of two equilibrating loop isomers, one of which contains a flipped-out cytosine. Our results indicate that the intercalative cytosine+-cytosine base pairs are not always necessary for an intramolecular I-motif. The dynamic character of the c-MYC I-motif is intrinsic to the NHE III1 sequence and appears to provide stability to the c-MYC I-motif.
Dai
Jixun
J
College of Pharmacy, The University of Arizona, Tucson, Arizona, United States of America.
Hatzakis
Emmanuel
E
Hurley
Laurence H
LH
Yang
Danzhou
D
D001483:Base Sequence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc