SNP-ChIP: A versatile and tag-free method to quantify changes in protein binding across the genome

Luis A. Vale-Silva, Tovah E. Markowitz, Andreas Hochwagen

Research output: Contribution to journalArticlepeer-review


Background: Chromatin-immunoprecipitation followed by sequencing (ChIP-seq) is the method of choice for mapping genome-wide binding of chromatin-associated factors. However, broadly applicable methods for between-sample comparisons are lacking. Results: Here, we introduce SNP-ChIP, a method that leverages small-scale intra-species polymorphisms, mainly SNPs, for quantitative spike-in normalization of ChIP-seq results. Sourcing spike-in material from the same species ensures antibody cross-reactivity and physiological coherence, thereby eliminating two central limitations of traditional spike-in approaches. We show that SNP-ChIP is robust to changes in sequencing depth and spike-in proportions, and reliably identifies changes in overall protein levels, irrespective of changes in binding distribution. Application of SNP-ChIP to test cases from budding yeast meiosis allowed discovery of novel regulators of the chromosomal protein Red1 and quantitative analysis of the DNA-damage associated histone modification γ-H2AX. Conclusion: SNP-ChIP is fully compatible with the intra-species diversity of humans and most model organisms and thus offers a general method for normalizing ChIP-seq results.

Original languageEnglish (US)
Article number54
JournalBMC Genomics
Issue number1
StatePublished - Jan 17 2019


  • ChIP-seq
  • Chromatin immunoprecipitation
  • Chromosomal proteins
  • Meiosis
  • Normalization
  • Post-translational modification
  • S. cerevisiae
  • Spike-in

ASJC Scopus subject areas

  • Biotechnology
  • Genetics


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