Fig. 6
Multiomics analysis reveals strong correlations between DNA methylation, chromatin accessibility and gene regulation during lens cell differentiation. A Scatter plot of the change in methylation (diff. methyl) of mCG DMRs mapped to the promoter or genebody of a DEG plotted against the change in chromatin accessibility. Red indicates a mCG DMR that is mapped to an upregulated/fiber cell gene. Blue indicates a mCG DMR that is mapped to a downregulated/epithelial cell gene. This plot is limited only to mCG DMRs that are mapped both to a chromatin-accessible region and either the promoter or genebody of a DEG. B Proportion of differentially methylated regions contained within the promoter or gene body of a DEG (upregulated/fiber cell gene or downregulated/epithelial cell gene) that is also contained within a differentially accessible chromatin region. Each site is categorized based on whether it has (1) increased or decreased mCG methylation during lens differentiation; (2) increased or decreased chromatin accessibility during lens differentiation, and (3) if the site is in the promoter or gene body of an epithelial cell preferred gene (RNAseq log2FC < − 0.4, q < 0.05) or a fiber cell preferred gene (RNAseq log2FC > 0.4, q < 0.05). This chart is limited only to mCG DMRs that are mapped to a differentially accessible chromatin region (ATACseq q < 0.05) and either the promoter or genebody of a DEG. Chi-square test p < 1 × 10–43. C Same as A but limited to the change in methylation (diff. methyl) of mCG DMRs that are mapped only to the promoter of a DEG and a chromatin-accessible region. Red indicates a mCG DMR that is mapped to an upregulated/fiber cell gene. Blue indicates a mCG DMR that is mapped to a downregulated/epithelial cell gene. D Same as B but limited to the change in methylation (diff. methyl) of mCG DMRs that are mapped only to the promoter of a DEG that is also in a differentially accessible chromatin region (ATACseq q < 0.05). Chi-square test p < 1 × 10–9. E Galgal6 UCSC genome browser track encompassing CRYBB1 and CRYBA4. Black bent arrows indicate transcription start sites. Vertical light blue highlighted column indicates the genomic region within the promoter region of both CRYBB1 and CRYBA4 that contains a mCG DMR that is significantly demethylated in fiber cells compared to epithelial cells. Also shown are tracks of the relative mCG methylation levels in epithelial cells (D13Epi_4_CG.bw) and fiber cells (D13_Fib_4_CG.bw). Tracks of ATACseq peak intensity from lens epithelial and fiber cells. Taller and wider peaks represent increased chromatin accessibility at the corresponding genomic region. Also shown are the relative gene expression changes expressed as fold change FPKM values of CRYBB1 and CRYBA4 in fiber cells compared to epithelial cells. F Same as C but for HSF4. Two mCG DMRs are shown. One in the promoter region (left) and one in the genebody (right). The relative gene expression changes expressed as fold change FPKM values of HSF4 in fiber cells compared to epithelial cells. G Same as C but for NOTCH2. Two mCG DMRs are shown. One in the promoter region (left) and one in the genebody (right). The relative gene expression changes of NOTCH2 are expressed as fold change FPKM values in epithelial cells compared to fiber cells