DMS-Seq for In Vivo Genome-wide Mapping of Protein-DNA Interactions and Nucleosome Centers

Cell Rep. 2017 Oct 3;21(1):289-300. doi: 10.1016/j.celrep.2017.09.035.


Protein-DNA interactions provide the basis for chromatin structure and gene regulation. Comprehensive identification of protein-occupied sites is thus vital to an in-depth understanding of genome function. Dimethyl sulfate (DMS) is a chemical probe that has long been used to detect footprints of DNA-bound proteins in vitro and in vivo. Here, we describe a genomic footprinting method, dimethyl sulfate sequencing (DMS-seq), which exploits the cell-permeable nature of DMS to obviate the need for nuclear isolation. This feature makes DMS-seq simple in practice and removes the potential risk of protein re-localization during nuclear isolation. DMS-seq successfully detects transcription factors bound to cis-regulatory elements and non-canonical chromatin particles in nucleosome-free regions. Furthermore, an unexpected preference of DMS confers on DMS-seq a unique potential to directly detect nucleosome centers without using genetic manipulation. We expect that DMS-seq will serve as a characteristic method for genome-wide interrogation of in vivo protein-DNA interactions.

Keywords: DNA-binding protein; chromatin; epigenome; gene regulatory network; genomic footprinting.

MeSH terms

  • Cell Line
  • Chromosome Mapping / instrumentation
  • Chromosome Mapping / methods*
  • DNA / genetics
  • DNA / metabolism
  • DNA Footprinting / methods*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Gene Library
  • Genetic Loci
  • Genome, Human*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • High-Throughput Nucleotide Sequencing
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Nucleosomes / chemistry*
  • Nucleosomes / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Sequence Analysis, DNA
  • Sulfuric Acid Esters / chemistry*


  • DNA-Binding Proteins
  • Histones
  • Nucleosomes
  • Sulfuric Acid Esters
  • DNA
  • dimethyl sulfate