Fig. 4
Stage-specific regulatory mechanisms of circRNAs and DNA methylation. a Heatmap shows the expression (log2(SRPBM+ 1)) of upregulated stage-specific circRNAs across developmental stages, and the bubble plot shows the top three enriched gene ontology (GO) terms for parental genes of the upregulated circRNAs across stages. b K-means clustering of all stage-specific circRNAs. Corresponding biological processes are shown next to each cluster. c Heatmap shows the DNA methylation signals (log2(FE + 1)) of stage-specific methylated regions (MRs) in promoters (1500 bp upstream and 500 bp downstream of transcriptional start sites, TSSs). FE, fold enrichment. The bubble plot shows the top five enriched gene ontology (GO) terms for genes with stage-specific MRs in promoter. d Distribution of DNA methylation levels around TSSs across all six skin developmental stages. e The methylation level of BRMS1 promoter decreases, whereas its expression level increases across developmental stages