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

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

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  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.


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.

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