Genome-wide mapping of in vivo protein-DNA interactions

Academic Article


  • In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these protein-DNA interactions comprehensively across entire mammalian genomes, we developed a large-scale chromatin immunoprecipitation assay (ChlPSeq) based on direct ultrahigh-throughput DNA sequencing. This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST, for repressor element-1 silencing transcription factor) to 1946 locations in the human genome. The data display sharp resolution of binding position [±S0 base pairs (bp)], which facilitated our finding motifs and allowed us to identify noncanonical NRSF-binding motifs. These ChlPSeq data also have high sensitivity and specificity [ROC (receiver operator characteristic) area > 0.96] and statistical confidence (P < 10-4), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development.
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Johnson DS; Mortazavi A; Myers RM; Wold B
  • Start Page

  • 1497
  • End Page

  • 1502
  • Volume

  • 316
  • Issue

  • 5830