MPE-seq, a new method for the genome-wide analysis of chromatin structure

The structure of chromatin is critical for processes such as transcription, DNA replication, and DNA repair. The most commonly used techniques for analyzing chromatin structure involve the use of enzymes such as micrococcal nuclease (MNase) and DNase I. These enzymes, however, have distinct characteristics that can at some times be an advantage but in other situations be a drawback. Here we describe methidiumpropyl-EDTA sequencing (MPE-seq), a method in which we use the chemical MPE-Fe(II) for the genome-wide analysis of chromatin structure. MPE-Fe(II) cleaves chromatin with minimal DNA sequence bias. Moreover, MPE-seq reveals noncanonical chromatin structures in active promoter regions that are not seen with standard MNase-seq conditions. MPE-seq provides insights into chromatin structure that complement the information gained from MNase-seq.