TY - JOUR UR - https://archiv.ub.uni-heidelberg.de/volltextserver/25916/ N2 - 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 ?-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. CY - London ; Berlin, Heidelberg A1 - Vale-Silva, Luis A. A1 - Markowitz, Tovah E. A1 - Hochwagen, Andreas SN - 1471-2164 IS - 54 KW - Chromatin immunoprecipitation KW - ChIP-seq KW - Spike-in KW - Normalization KW - Chromosomal proteins KW - Post-translational modification KW - Meiosis KW - S. cerevisiae Y1 - 2019/// PB - BioMed Central ; Springer EP - 10 VL - 20 ID - heidok25916 AV - public JF - BMC Genomics SP - 1 TI - SNP-ChIP: a versatile and tag-free method to quantify changes in protein binding across the genome ER -