Extended Data Fig. 3. H3K27me3 is globally enriched in TSCs compared to ESCs.
a) Compartments as defined by Hi-C (PC1 eigenvector, A > 0, B < 0) comparing ESCs and TSCs for the first five chromosomes. Few regions switch compartments and the overall distributions are highly comparable. b) Hi-C contact frequencies for ESCs and TSCs for chromosome 1 (100 kb bins), used to generate the comparative heatmap in Fig. 2a (two merged technical replicates per cell type). c) Comparison of contact frequencies across genomic distances between ESCs and TSCs. TSCs show an increase in very long-range contacts, but the effect is very small and imprecise. d) Density plots comparing DNA methylation and histone modification levels in one kb genomic tiles as measured using quantitative MINUTE-ChIP (log2 fold change over input, n = three merged biological replicates per cell type). TSC epigenomes are characterized by lower DNA methylation and higher K27me3. e) Western blot showing an increase of H3K27me3 in TSCs compared to ESCs. f) log2 fold change of modified histone tails measured by mass spectrometry (n = three TSC biological replicates normalized against the mean of two biological ESC replicates). Histone tails carrying H3K27me3 are enriched in TSCs compared to ESCs, whereas unmodified K27 residues are depleted. g) Heatmaps of DNA methylation and histone signal across different genomic features for ESCs and TSCs. TSCs exhibit higher H3K27me3 levels across all feature groups including flanking genomic regions. ESCs show a higher H3K4me3 signal at protein-coding promoters. In contrast, TSCs show an increase of this active modification at full length IAP elements, which is accompanied by an increase in their expression (bottom right). Notably, H3K27me3 also appears to have specific enrichment at the promoters of these elements in TSCs, whereas H2AK119ub1 is present in both cell types. H2AK119ub1 levels appear to be increased in ESCs at CGIs and promoters.