To gain insight into possible sequence determinants of the distinct PU.1 binding patterns observed in macrophages and B cells, we examined promoter-proximal and distal regions that were either commonly or cell type-specifically bound by PU.1 for enriched sequence elements by de novo motif analysis. The most enriched motifs were nearly identical in each of the different subsets and resembled the known PU.1 consensus element (Figure 2A and Figure S2A). The only exception was found at proximal promoter peaks common to both cell types, where PU.1 likely competes for binding with ETS factors, such as GABPα, at related ETS sites found in CpG islands (Xie et al., 2005). While nearly 60% of all PU.1 peaks contain either the PU.1 or GABP version of ETS motifs, the most enriched motif in the remaining peaks was a degenerate ETS core motif (RRGGAASY). Overall, ~85% of all PU.1 peaks contain an ETS site, strongly suggesting that PU.1 binds directly to the vast majority of its DNA target sites (Figure 2A and Table S2)
