NMR studies of DNA support the role of pre-existing minor groove variations in nucleosome indirect readout

Biochemistry. 2014 Sep 9;53(35):5601-12. doi: 10.1021/bi500504y. Epub 2014 Aug 26.

Abstract

We investigated how the intrinsic sequence-dependent properties probed via the phosphate linkages (BI ↔ BII equilibrium) influence the preferred shape of free DNA, and how this affects the nucleosome formation. First, this exploits NMR solution studies of four B-DNA dodecamers that together cover 39 base pairs of the 5' half of the sequence 601, of special interest for nucleosome formation. The results validate our previous prediction of a systematic, general sequence effect on the intrinsic backbone BII propensities. NMR provides new evidence that the backbone behavior is intimately coupled to the minor groove width. Second, application of the backbone behavior predictions to the full sequence 601 and other relevant sequences demonstrates that alternation of intrinsic low and high BII propensities, coupled to intrinsic narrow and wide minor grooves, largely coincides with the sinusoidal variations of the DNA minor groove width observed in crystallographic structures of the nucleosome. This correspondence is much poorer with low affinity sequences. Overall, the results indicate that nucleosome formation involves an indirect readout process implicating pre-existing DNA minor groove conformations. It also illustrates how the prediction of the intrinsic structural DNA behavior offers a powerful framework to gain explanatory insight on how proteins read DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA, B-Form / chemistry*
  • DNA, B-Form / genetics
  • Humans
  • Macromolecular Substances / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nucleic Acid Conformation
  • Nucleosomes / chemistry*
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / genetics

Substances

  • DNA, B-Form
  • Macromolecular Substances
  • Nuclear Proteins
  • Nucleosomes
  • Oligodeoxyribonucleotides