Fig. 5

Higher-order topological changes follow epigenetic but not transcriptional changes. a Normalized Hi-C interaction heatmap showing chromatin compartmentalization (A/B compartments) at 100 kb resolution for chromosome 1 in wild-type (WT; left) versus TKO cells (right). Coefficients of the first principal component (PC1) of the Hi-C interaction heatmap are plotted on top along the linear sequence of chromosome 1, showing no apparent changes in chromatin compartment organization upon H1 depletion in mouse ES cells. b PE-SCAN Hi-C analysis probing Hi-C interactions between clusters of binding sites for transcription factors that control mouse ES cell identity (pluripotency factors). ES cell-specific interactions among binding sites of Oct4, Nanog, and Klf4 remain present in mouse ES cells upon depletion of H1 in TKO cells. c Plot comparing the distribution of Hi-C interactions versus genomic distance for three different Hi-C maps. Mouse ES cells are characterized by a relatively large fraction of interactions over short distances, whereas differentiation is known to be accompanied by an increase in long-range interactions. The TKO Hi-C map clearly shows a shift towards those of a more differentiated cell. d Percentages of genes in groups of TADs ranked according to the Hi-C domain score in WT ES cells. The ranking on the x-axis is such that the leftmost group contains the 20 % TADs with the lowest and the rightmost group of TADs contains the highest Hi-C domain scores. We also show the distribution of sites, in WT ES cells, enriched for the histone marks H3K4me1and H3K4me3, sites with DNA methylation and DHSs in these groups of TADs. e Boxplots comparing the Hi-C domain score of all mouse ES cell TADs in our WT and TKO Hi-C maps. A two-sample Wilcoxon rank sum test was applied to test the significance of the shift in domain score in TKO cells (p value < < 1e-6). f Percentages of the total sum of all epigenetic changes in groups of TADs ranked according to the difference in Hi-C domain score between TKO and WT ES cells. The ranking on the x-axis is such that the leftmost group contains the 20 % TADs with the lowest and the rightmost group of TADs contains the highest difference in Hi-C domain score. We also show the percentages for the individual changes in the histone marks H3K4me1and H3K4me3, differential DNA methylation and differential DNase I hypersensitivity