Recent studies have demonstrated that lineage-determining transcription factors preferentially associate with genomic regions marked by cell type-specific patterns of histone modifications, such as monomethylation of H3K4 (H3K4me1), that are suggested to signify accessible chromatin and/or enhancer-like elements (Heintzman et al., 2009). In addition, trimethylation of H3K4 (H3K4me3) marks active and/or poised promoters (Kim et al., 2005). We therefore profiled H3K4me1 and H3K4me3 in both macrophages and B cells using ChIP-Seq and found that the majority (>80%) of PU.1-bound sites were associated with either promoter-proximal H3K4me3 or distal H3K4me1 in both cell types. Cell-specific binding of PU.1 at distal sites was highly associated with cell-specific H3K4me1 (Figure 4A). Analysis of the genomic distribution of the H3K4me1 signal averaged for all distal PU.1 binding sites revealed a bimodal pattern with a pronounced reduction of signal centered over the PU.1 binding site (Figure 4B), analogous to that recently described for H3K4me1 around promoter-distal FoxA2- and STAT1-bound sites in mouse liver and HeLa cells, respectively (Robertson et al., 2008). Similarly, 80% of distal Oct-2 and C/EBP sites were marked by a corresponding pattern of cell-specific H3K4me1 (Figure 4B).
