Fig. 5 Loss of DNA methylation causes ectopic activation of putative adult enhancers and aberrant acquisition of distal H3K4me3 in early embryos.(A) Pie charts showing distributions of promoter (blue) and distal (red) H3K4me3 sites in control and mKD embryos at shield stage. (B) UCSC Genome Browser snapshot showing H3K4me3 at dome and shield stages of control (blue) and dnmt1 mKD (red) embryos, and CG density. Arrows indicate ectopic H3K4me3 sites. (C) Heatmaps showing distal H3K4me3, mCG, H3K27ac, H3K4me1, open chromatin (ATAC-seq), and CG density in either control or dnmt1 mKD embryos. Peaks were classified into three clusters based on the dynamics of distal H3K4me3: lost (H3K4me3 lost in dnmt1 mKD embryos, blue), ectopic (H3K4me3 acquired in dnmt1 mKD embryos, red), and retained (H3K4me3 present in both control and mKD, green). (D) UCSC Genome Browser snapshots showing H3K4me3, mCG, H3K27ac, H3K4me1, and open chromatin (ATAC-seq) at dome and shield stages of control (blue) and dnmt1 mKD (red) embryos and adult tissues (spleen, left; skin, middle; muscle, right) (45). Green shadow indicates promoter, and orange shadow indicates putative enhancer.
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