Model of cell type-specific and broadly active enhancers. (A) Model for motif requirements of enhancer sequences. DRMs and motifs for cell type-specific TFs such as GATA, E-box, or Fkh motifs are required for cell type-specific enhancer activity (middle). Broadly active enhancers contain a higher number of DRMs, as depicted by DRMsn (bottom). These differences in motif content are sufficient to discriminate between enhancer classes and between enhancers and negative regions (top). (B) Enrichment and depletion of DRMs in human regulatory regions defined by DNase I hypersensitive sites (DHS) (left) (Thurman et al. 2012) and by H3K4me1 and H3K27ac (right) (The ENCODE Project Consortium 2012). (C) Luciferase assays in HeLa cells of three human enhancers (light green) and variants in which all instances of one type of DRM are mutated (dark green). Error bars indicate standard deviations of three independent biological replicates. Shown are P-values from unpaired t-tests.
