Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position

Nat Methods. 2013 Dec;10(12):1213-8. doi: 10.1038/nmeth.2688. Epub 2013 Oct 6.


We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • Cell Separation
  • Chromatin / chemistry
  • Computational Biology / methods
  • DNA-Binding Proteins / chemistry*
  • Dimerization
  • Enhancer Elements, Genetic
  • Epigenomics*
  • Flow Cytometry / methods
  • Humans
  • Interleukin-2 / genetics
  • Nucleosomes / chemistry*
  • Polymerase Chain Reaction / methods
  • Transcription Factors / chemistry


  • Chromatin
  • DNA-Binding Proteins
  • Interleukin-2
  • Nucleosomes
  • Transcription Factors