Abstract
We describe a high-throughput method, named ChIP-SNP, for the identification of allele-specific protein-DNA interactions throughout the human genome. ChIP-SNP combines chromatin immunoprecipitation (ChIP) with whole-genome single nucleotide polymorphism (SNP) genotyping microarray analysis. We demonstrated that it can be used to accurately identify allele-specific binding of RNA polymerase II (RNAP) in the human fibroblast genome, uncovering imprinted genes and other allele-specific binding events. ChIP-SNP will facilitate the study of mechanisms of allele-specific gene expression.
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Acknowledgements
We thank T.H. Kim for technical advice; K. Ching, E. Ke, L.O. Barrera, H. Xi and Z. Weng for their assistance and feedback during the course of this project, and members of Ren Lab for their helpful discussions. This work is supported by funding from Ludwig Institute for Cancer Research (B.R.) and US National Institutes of Health (B.R.).
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N.D.M., J.C. and R.K.S. conducted the ChIP-SNP experiments; N.D.M. and J.C. performed the allele-specific expression experiments; N.D.M. performed the sequencing validation, and analyzed the ChIP-SNP, ASE and sequencing data; N.D.M., J.-B.F. and B.R. conceived and designed the experiments; N.D.M. and B.R. wrote the manuscript.
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J.C. and J.-B.F. are employees of Illumina, Inc., which may benefit from the publication of this manuscript.
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Supplementary Figures 1–2, Supplementary Tables 1–6, Supplementary Methods (PDF 1361 kb)
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Maynard, N., Chen, J., Stuart, R. et al. Genome-wide mapping of allele-specific protein-DNA interactions in human cells. Nat Methods 5, 307–309 (2008). https://doi.org/10.1038/nmeth.1194
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DOI: https://doi.org/10.1038/nmeth.1194
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