The effect of MNase on nucleosome positioning data

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 sequence-dependent models for nucleosome positioning based on such data. Thus, sequencing data generated after MNase digestion of chromatin requires a control experiment in order to determine nucleosome positions.