Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Genome-wide mapping of allele-specific protein-DNA interactions in human cells

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: ChIP-SNP analysis of RNAP binding in human fibroblasts.
Figure 2: Validation of RNAP ChIP-SNP results by sequencing.

Similar content being viewed by others

References

  1. Wood, A.J. & Oakey, R.J. PLoS Genet. 2, e147 (2006).

    Article  Google Scholar 

  2. Chow, J.C., Yen, Z., Ziesche, S.M. & Brown, C.J. Annu. Rev. Genomics Hum. Genet. 6, 69–92 (2005).

    Article  CAS  Google Scholar 

  3. Gimelbrant, A., Hutchinson, J.N., Thompson, B.R. & Chess, A. Science 318, 1136–1140 (2007).

    Article  CAS  Google Scholar 

  4. Knight, J.C. Trends Genet. 20, 113–116 (2004).

    Article  CAS  Google Scholar 

  5. Hudson, T.J. Nat. Genet. 33, 439–440 (2003).

    Article  CAS  Google Scholar 

  6. Ren, B. et al. Science 290, 2306–2309 (2000).

    Article  CAS  Google Scholar 

  7. Bulyk, M.L. Curr. Opin. Biotechnol. 17, 422–430 (2006).

    Article  CAS  Google Scholar 

  8. Knight, J.C., Keating, B.J., Rockett, K.A. & Kwiatkowski, D.P. Nat. Genet. 33, 469–475 (2003).

    Article  CAS  Google Scholar 

  9. Kadota, M. et al. PLoS Genet. 3, e81 (2007).

    Article  Google Scholar 

  10. McCann, J.A. et al. BMC Genomics 8, 322 (2007).

    Article  Google Scholar 

  11. Seitz, H. et al. Genome Res. 14, 1741–1748 (2004).

    Article  CAS  Google Scholar 

  12. Luedi, P.P., Hartemink, A.J. & Jirtle, R.L. Genome Res. 15, 875–884 (2005).

    Article  CAS  Google Scholar 

  13. Pollard, K.S. et al. Hum. Genet. 122, 625–634 (2008).

    Article  CAS  Google Scholar 

  14. Zeitlinger, J. et al. Nat. Genet. 39, 1512–1516 (2007).

    Article  CAS  Google Scholar 

  15. Muse, G.W. et al. Nat. Genet. 39, 1507–1511 (2007).

    Article  CAS  Google Scholar 

Download references

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.).

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Bing Ren.

Ethics declarations

Competing interests

J.C. and J.-B.F. are employees of Illumina, Inc., which may benefit from the publication of this manuscript.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–2, Supplementary Tables 1–6, Supplementary Methods (PDF 1361 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.1194

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing