Fig. 3

Epigenetic changes accumulate in gene-dense TADs. a Ratio of (the percentage of) sites with a significant loss of DHSs in TKO cells, over the (percentage of) DHSs in wild-type (WT) ES cells in groups of TADs. The TADs are ordered based on gene content and grouped in equally sized bins (same ordering as in Fig. 1d), with the most gene poor TADs on the left. An analogous ratio is plotted for the sites that lose H3K4me3 in TKOs, but here the ratio is computed relative to the WT sites with H3K4me3 enrichment. b Same as panel (a), but for sites that significantly lose H3K4me1 enrichment in TKO cells (with the ratio compared relative to the WT H3K4me1 sites). c Percentages of de novo DHSs in groups of TADs ranked according to the number of overlapping genes (same ranking as in (a, b)). Also shown are the percentages of de novo H3K4me1 sites in TKO ES cells. d Example of two loci, one on chromosome 12 and one on chromosome 8, where several novel DHSs appear which co-occur with changes in H3K4me1 in TKO ES cells (highlighted in grey). Normalized DNase-seq coverage is plotted in green (averaged over triplicate experiments in WT and TKO) and normalized H3K4me1 ChIP-seq coverage is plotted in red (averaged over duplicates). Black boxes indicate genes and a track containing the different computationally predicted chromatin states in WT mouse ES cells (chromHMM) is shown as a reference