The effect of micrococcal nuclease digestion on nucleosome positioning data

PLoS One. 2010 Dec 29;5(12):e15754. doi: 10.1371/journal.pone.0015754.


Eukaryotic genomes are packed into chromatin, whose basic repeating unit is the nucleosome. Nucleosome positioning is a widely researched area. A common experimental procedure to determine nucleosome positions involves the use of micrococcal nuclease (MNase). Here, we show that the cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments. This strongly affects nucleosome positioning data and especially sequence-dependent models for nucleosome positioning. As a consequence we see a need to re-evaluate whether the DNA sequence is a major determinant of nucleosome positioning in vivo. More generally, our results show that data generated after MNase digestion of chromatin requires a matched control experiment in order to determine nucleosome positions.

MeSH terms

  • Algorithms
  • Chromatin / chemistry
  • Codon
  • Computational Biology / methods
  • DNA / chemistry
  • DNA, Fungal / genetics
  • Databases, Protein
  • Dimerization
  • Genome, Fungal
  • Micrococcal Nuclease / metabolism*
  • Nucleosomes / chemistry*
  • Nucleosomes / metabolism
  • Nucleosomes / ultrastructure
  • Pattern Recognition, Automated / methods
  • Ribonuclease, Pancreatic / chemistry
  • Saccharomyces cerevisiae / genetics*
  • Sequence Analysis, DNA


  • Chromatin
  • Codon
  • DNA, Fungal
  • Nucleosomes
  • DNA
  • Ribonuclease, Pancreatic
  • Micrococcal Nuclease