I-motif structures formed in the human c-MYC promoter are highly dynamic--insights into sequence redundancy and I-motif stability

PLoS One. 2010 Jul 19;5(7):e11647. doi: 10.1371/journal.pone.0011647.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Humans
  • Magnetic Resonance Spectroscopy
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc