ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions

Methods. 2009 Jul;48(3):240-8. doi: 10.1016/j.ymeth.2009.03.001. Epub 2009 Mar 9.


Chromatin immunoprecipitation (ChIP) allows specific protein-DNA interactions to be isolated. Combining ChIP with high-throughput sequencing reveals the DNA sequence involved in these interactions. Here, we describe how to perform ChIP-seq starting with whole tissues or cell lines, and ending with millions of short sequencing tags that can be aligned to the reference genome of the species under investigation. We also outline additional procedures to recover ChIP-chip libraries for ChIP-seq and discuss contemporary issues in data analysis.

MeSH terms

  • Cells, Cultured
  • Chromatin / chemistry
  • Chromatin Immunoprecipitation / methods*
  • Cross-Linking Reagents / chemistry
  • Formaldehyde / chemistry
  • Humans
  • Polymerase Chain Reaction / methods
  • Protein Interaction Mapping / methods
  • Sequence Analysis, DNA / methods*


  • Chromatin
  • Cross-Linking Reagents
  • Formaldehyde