De novo motif discovery of TF motifs in Hoxa9 and Meis1 binding sites and comparison to previously characterized macrophage enhancer sequences. (A) Six de novo DNA sequence motifs and their STAMP logos29 and enrichment statistics, including observed frequencies and similarity measures. A complete list of de novo motifs (n = 15) is given in supplemental Figure 5. (B) Spatial distributions of motifs listed in A with respect to centers of H/M binding sites. (C) Comparison of normalized ChIP-chip signal of 6 TFs at H/M binding sites that are cooccupied by C/EBPα (red), PU.1 (blue), or both C/EBPα+PU.1 factors.42 In most cases (except HOXA9 and STAT5), H/M peaks that are cobound by C/EBPα showed highest expression intensity (red line), followed by C/EBPα+PU.1 (black line) and PU.1 (blue line). Similarly, the ChIP-chip signal at 60 randomly selected control regions is depicted by the gray line. (D) A large proportion of H/M peaks were found to overlap with enhancer sequences bound by C/EBPα (red), PU.1 (blue), or both C/EBPα+PU.1 (black) in lipopolysaccharide-stimulated macrophages.43 (E) Comparative motif enrichment analysis showed increased level enrichment of HOXA, PBX/MEIS1, and STAT motifs in the set of enhancers described by Heinz et al43 that are bound by Hoxa9 (green) and Meis1 (blue), but not in those that are not associated with Hoxa9 and Meis1 (red).
