Protein-binding regions lacking high or moderate affinity cognate recognition sites have 21% lower median scores by rank than regions with recognition sequences (Wilcoxon rank sum p-value < 10−16). 82% of the low-signal regions have high-affinity recognition sequences for other factors. In addition, when ChIP-seq peaks are ranked by their concordance with their known recognition sequence, the median DNase I accessibility is two-fold higher in the bottom 20% of peaks than in the upper 80% (Genome Structure Correction20, GSC p-value <10−16) consistent with previous observations21–24. We speculate that low signal regions are either lower-affinity sites21 or indirect TF target regions associated through interactions with other factors (see also refs 25,26).
