Tehranchi, A.K. et al. Cell 165, 1–12 (2016).

It is straightforward to find the genome-wide binding sites of transcription factors (TFs) using chromatin immunoprecipitation (ChIP), but it remains somewhat difficult to predict how single-nucleotide variants (SNVs) affect such binding. Tehranchi et al. devised a pooling-based ChIP-seq approach to find binding quantitative trait loci (bQTLs). Comparing allele frequency in the pool before and after ChIP allowed the researchers to identify alleles with high or low affinity for a TF. Looking at five TFs in a pool of 60 human cell lines, they identified 3% of SNVs as bQTLs. Some bQTLs change the binding of pioneer factors, such as CTCF, which regulates chromatin structure, and thus these bQTLs also affect the recruitment of other TFs as well as long-range chromatin interactions.