Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity

Nat Commun. 2018 Nov 2;9(1):4590. doi: 10.1038/s41467-018-07115-y.


Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Hypoxia / genetics
  • Cell Line, Tumor
  • Chromatin / metabolism
  • DNA / genetics*
  • Environment*
  • Epigenesis, Genetic
  • Epigenomics*
  • Epithelial Cell Adhesion Molecule / metabolism
  • Epitopes / metabolism*
  • Lymphocytes / metabolism
  • Mice
  • Nucleotide Motifs / genetics
  • Proteins / metabolism*
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Single-Cell Analysis*
  • Transcription Factors / metabolism
  • Transposases / metabolism


  • Chromatin
  • Epithelial Cell Adhesion Molecule
  • Epitopes
  • Proteins
  • Transcription Factors
  • DNA
  • Transposases