Extended Data Fig. 5: Characterization of lineage-specific H3K27ac and H3K4me3 ChIP–seq data.

a, Percentage of peaks overlapping promoters (±500 bp of TSS of annotated mRNAs (Ensembl v.87); lighter colour) and not overlapping promoters (distal peaks, darker colour). H3K27ac peaks tend to be distal from the promoters, marking putative enhancer elements⁵³. H3K4me3 peaks tend to overlap promoter regions, marking TSS⁵⁴. b, Venn diagrams showing overlap of peaks for each lineage, for distal H3K27ac (left) and H3K4me3 (right). This shows that H3K27ac peaks tend to be lineage-specific, whereas H3K4me3 peaks tend to be shared between lineages. c, Illustrative example of the ChIP–seq profile for the ectoderm marker Cxcl12. The top tracks show wiggle plots of ChIP–seq read density (normalized by total read count) for lineage-specific H3K27ac and H3K4me3. The coding sequence is shown in black. The bottom tracks show the lineage-specific peak calls (Methods). H3K27ac peaks are split into distal (putative enhancers) and proximal to the promoter. d, Left, bar plot of the fraction of E7.5 lineage-specific enhancers (n = 691 for ectoderm, 618 for endoderm and 340 for mesoderm) that are uniquely marked by H3K27ac in either E10.5 midbrain, E12.5 gut or E10.5 heart. Right, heat map displaying H3K27ac levels at individual lineage-specific enhancers (n = 2,039 for ectoderm, 1,124 for endoderm and 631 for mesoderm) in more differentiated tissues. E7.5 enhancers are predominantly marked in their differentiated-tissue counterparts (midbrain for ectoderm, gut for endoderm and heart for mesoderm).