(A) Browser images showing examples of rod hypo-DMRs that are enriched for active enhancer histone marks in fetal E14.5 brain (from Shen et al., 2012) but not in adult rods. These rod hypo-DMRs also display low levels of DNA methylation in both WT rods and fetal E13 cerebral cortex (from Lister et al., 2013), but not in cones or in most adult cortical neuron types (Exc, PV, VIP; from Mo et al., 2015). In addition, rd7 rods show higher levels of methylation than WT rods but lower levels than cones. (B) Cone hypo-DMRs show a six-fold higher overlap with ATAC-seq peaks, compared to rod hypo-DMRs with rod ATAC-seq peaks. (C–G) Heatmap showing CG methylation levels in a 3 kb window centered at rod and cone hypo-DMRs (C). At the same genomic regions, the following were plotted: ATAC-seq signal (D), ChIP-seq signals for histone modifications in adult rods (this study) or in E14.5 fetal brain (from Shen et al., 2012) (E), and ChIP-seq signals for retinal TFs (from Corbo et al., 2010; Hao et al., 2012; Samuel et al., 2014) (F). The density of DMRs relative to their closest TSS is shown in (G) for a 100 kb window around the TSS. For (C–G), the rows are ordered by decreasing rank of the absolute signals of rod and cone ATAC-seq data at rod and cone hypo-DMRs, respectively. (H) The fetal cortex shares low CG DNA methylation with rods at a substantial fraction of rod hypo-DMRs (top), but shows high methylation at the majority of cone hypo-DMRs (bottom). Furthermore, methylation levels in rd7 rods are generally intermediate between WT rods and cones, particularly at rod hypo-DMRs.