In vivo characterization of regulatory polymorphisms by allele-specific quantification of RNA polymerase loading

Nat Genet. 2003 Apr;33(4):469-75. doi: 10.1038/ng1124. Epub 2003 Mar 10.


In vivo characterization of regulatory polymorphisms is a key requirement for next-generation human genetic analysis. Here we describe haploChIP, a method that uses chromatin immunoprecipitation (ChIP) and mass spectrometry to identify differential protein-DNA binding in vivo associated with allelic variants of a gene. We demonstrate this approach with the imprinted gene SNRPN. HaploChIP showed close correlation between the level of bound phosphorylated RNA polymerase II at the SNRPN locus and allele-specific expression. Application of the approach to the TNF/LTA locus identified functionally important haplotypes that correlate with allele-specific transcription of LTA. The haploChIP method may be useful in high-throughput screening for common DNA polymorphisms that affect gene regulation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Autoantigens
  • Cell Line
  • Chromatin / metabolism
  • Genetic Techniques*
  • Genomic Imprinting*
  • Genotype
  • Haplotypes
  • Humans
  • Mass Screening
  • Mass Spectrometry
  • Models, Genetic
  • Phosphorylation
  • Polymorphism, Genetic*
  • Precipitin Tests
  • Protein Binding
  • RNA Polymerase II / metabolism*
  • Ribonucleoproteins, Small Nuclear / genetics*
  • Time Factors
  • Transcription, Genetic
  • snRNP Core Proteins


  • Autoantigens
  • Chromatin
  • Ribonucleoproteins, Small Nuclear
  • SNRPN protein, human
  • snRNP Core Proteins
  • RNA Polymerase II