Hoxa9 and Meis1 binding sites show high regulatory potential and carry the epigenetic signature of enhancer sequences. (A) Regulatory potential scores are high at the center of Hoxa9 and Meis1 binding with correlation of 0.81 (P < .0001). The lines depict average of regulatory potential scores (blue) and sequencing reads in a ± 4-kb region centered at Hoxa9 and Meis1 binding sites. (B) Spatial distribution of epigenetic modifications surrounding high-confidence Hoxa9 and Meis1 binding sites. Epigenetic modification status was examined in ± 4-kb regions centered on Hoxa9 and Meis1 binding loci with the use of a custom Nimblegen tiling array. The normalized log₂ ratios of a modification marker over input are shown relative to the center of the binding sites. (C) Spatial distribution of epigenetic modifications at the promoter region (+ 1 kb upstream and − 2 kb downstream) of a selected set of 360 genes that are closest to Hoxa9 and Meis1 binding sites. The normalized log₂ ratio of a modification marker over input are shown for each nucleotide with respect to their distance to the transcription start sites. (D) The 3-dimensional projection of 7 epigenetic modification markers at the Hoxa9 and Meis1 binding sites with the use of principal component analysis. The first 3 principal components account for 82.1% of the total variance. The figure shows the loadings of each epigenetic modification on these components. The p300, CBP, H3K4me1 epigenetic signature that is characteristic of enhancer sequences includes > 65% of all Hoxa9 and Meis1 binding sites.