DMS-seq for in vivo genome-wide mapping of protein–DNA interactions and nucleosome centers

Dimethyl sulfate (DMS) is a methylating reagent that has long been used to detect footprints of DNA-bound proteins in vitro as well as in vivo. Here we describe DMS-seq for in vivo genome-wide mapping of protein-DNA interactions. DMS-seq exploits the cell-permeable nature of DMS to obviate the need for nuclear isolation, thereby simplifying the process to detect binding sites of transcription factors. Furthermore, we found that DMS preferentially attacks nucleosome centers in vivo, evidencing for DMS-seq as a first method that locates them without using genetically-modified histones and is hence applicable to any eukaryote. DMS-seq should be a simple and unique method in epigenomics.