The striking association of PU.1 and collaborating lineage-determining transcription factors with cell-specific H3K4me1 in macrophages and B cells led us to perform a de novo motif analysis of the approximately 20000 distal genomic regions that were focally marked by H3K4me1 in each cell type. This analysis revealed that these regions in macrophages were most highly enriched for PU.1, AP-1, C/EBP and RUNX motifs (Figure 4E), while H3K4me1-marked regions in B cells displayed maximal enrichment for PU.1, E2A, OCT, EBF and RUNX motifs (Figure S4C). This computational result is supported by ChIP-Seq data demonstrating that the majority (70%) of the H3K4me1-positive regions in macrophages were bound by PU.1 and/or C/EBPβ (Figure 4F) and is consistent with the finding that PU.1 (and likely C/EBP) binding can induce H3K4me1 deposition. Of note, analysis of the genome-wide location of p300 in resting macrophages (Ghisletti et al., 2010) indicates marked enrichment at genomic locations co-bound by PU.1 and C/EBPβ (Figure 4G).
