Fig. 1

Identification of hypo-enhancers. a Heat map displaying H3K27Ac and DNA methylation at enhancers, called by being H3K4me1-positive and H3K4me3-negative at 4 hpf. The heat map was first sorted on DNA methylation, split (yellow dashed line), and independently sorted on H3K27ac. b Genome browser view of a hyper-enhancer close to the TSS of sox2. ChIP-Seq data and DNA methylation data are displayed for embryos 4 hpf. Normalized ChIP-Seq enrichments and fractional methylation are indicated at the left side of the image. The blue box indicates the hyper-enhancer. The blue arrow indicates the orientation of the gene. Blue horizontal bars indicate HMRs. c Genome browser view of a hypo-enhancer close to the TSS of tlx3b. ChIP-Seq data and DNA methylation data are displayed for embryos 4 hpf. Normalized ChIP-Seq enrichments and fractional methylation are indicated at the left side of the image. The blue box indicates the hypo-enhancer. The blue arrow indicates the orientation of the gene. Blue horizontal bars indicate HMRs. d The overlap of the hypo- and hyper-enhancers with H3K27ac at the indicated developmental time points (*p < 2.2 × 10⁻¹⁶, hyper geometric distribution). e The overlap of the hypo- and hyper-enhancers with three TFs at 4 hpf (*p < 2.2 × 10⁻¹⁶, hyper geometric distribution). f Molecular Gene Ontology terms associated with hypo-enhancers using the GREAT tool. Significance score for enrichment is given on the x-axis. FDR false discovery rate