ChIP-seq and beyond: new and improved methodologies to detect and characterize protein-DNA interactions

Nat Rev Genet. 2012 Dec;13(12):840-52. doi: 10.1038/nrg3306. Epub 2012 Oct 23.


Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) detect protein-DNA binding events and chemical modifications of histone proteins. Challenges in the standard ChIP-seq protocol have motivated recent enhancements in this approach, such as reducing the number of cells that are required and increasing the resolution. Complementary experimental approaches - for example, DNaseI hypersensitive site mapping and analysis of chromatin interactions that are mediated by particular proteins - provide additional information about DNA-binding proteins and their function. These data are now being used to identify variability in the functions of DNA-binding proteins across genomes and individuals. In this Review, I describe the latest advances in methods to detect and functionally characterize DNA-bound proteins.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation / methods*
  • Chromatin Immunoprecipitation / standards
  • Chromatin Immunoprecipitation / trends
  • DNA / genetics
  • DNA / metabolism
  • DNA Footprinting
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Histones / metabolism
  • Humans
  • Protein Binding
  • Sequence Analysis, DNA / methods
  • Sequence Tagged Sites


  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • DNA