%0 Journal Article
%@ 1471-2164
%A Vale-Silva, Luis A.
%A Markowitz, Tovah E.
%A Hochwagen, Andreas
%C London ; Berlin, Heidelberg
%D 2019
%F heidok:25916
%I BioMed Central ; Springer
%J BMC Genomics
%K Chromatin immunoprecipitation, ChIP-seq, Spike-in, Normalization, Chromosomal proteins, Post-translational modification, Meiosis, S. cerevisiae
%N 54
%P 1-10
%T SNP-ChIP: a versatile and tag-free method to quantify changes in protein binding across the genome
%U https://archiv.ub.uni-heidelberg.de/volltextserver/25916/
%V 20
%X 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.