Monocyte subset-specific active enhancer signatures. (A) Bubble-plot representation of CAGE-TSS activity around subset-specific enhancer candidate regions showing at least 3-fold different H3K27ac signals. The bubble plots encode 3 quantitative parameters per CAGE cluster: distance from the putative enhancer, log₁₀ of fold change in CAGE cluster tag count between classical and nonclassical monocytes (y-axis), and the absolute CAGE cluster tag count of the monocyte subset with the highest expression level (bubble diameter). There is a clear bias for the putative enhancer elements to associate with CAGE clusters upregulated in the corresponding cell type (P < .001, Wilcoxon signed-rank test). (B) Putative subset-specific enhancer region of the human CD14 locus. On top, UCSC Genome Browser tracks covering the entire CD14 locus are shown including epigenetic data (H3K4me1 and H3K27ac), positions of transcription factor binding sites for PU.1 and C/EBPβ in total monocytes,¹⁸  positions of bidirectional enhancers identified from the FANTOM5 expression atlas,⁴⁴  HeliScopeCAGE data (monocyte subsets are indicated by coloring: classical, red; intermediate, green; nonclassical, blue), GencodeV10 gene annotation, 5′-RACE–based annotation of a novel TMOC6 transcript, and positions of genomic intervals that were used for enhancer reporter assays. The bottom panel shows relative luciferase activities (enhancer construct/CD14 promoter only [control]) of individual enhancer constructs in a monocytic (THP-1) and a T-cell (Jurkat) cell line. A myeloid-specific set of CD14 enhancers was detected between regions 6 and 8.