Extended Data Figure 2: Structure of the Xa chromosome in ES cells, compartment analysis and characterization of interactions between genes that escape XCI.

a, Allele-specific Hi-C contact maps for X chromosome in ES cells at 500-kb resolution (top), and for a ~40-Mb region centred around the DXZ4-containing locus at 40-kb resolution (bottom). The insulation score is plotted at the bottom of each 40-kb heat map as in Fig. 1a. Purple shaded areas indicate the IQR of insulation scores along the chromosome. b, Zoomed in view of three regions showing Hi-C interactions, RNA-seq and ATAC–seq signal on the Cast and 129 Xa chromosomes in ES cells. c, Compartment profiles of X chromosome in ES cells and NPCs. The first eigenvector (PC1) of each allele-specific Hi-C contact map, obtained with principal component analysis, is shown, together with the difference in chromosome-wide insulation score between the 129 and Cast allele. A/B-compartments are evident in ES cells and NPCs along both Xa (red and blue signal), whereas the first eigenvector corresponds to the two mega-domains for the Xi chromosome in NPCs. In ES cells, both Xa chromosomes display comparable insulation profiles (difference is close to 0 along the chromosome), whereas in NPCs large differences are observed (difference in insulation fluctuates along the chromosome). Grey areas indicate regions with low SNP density that were excluded from analysis. d, Same plots as in Fig. 2e for the same set of genes that escape XCI in NPCs, but using Hi-C data obtained in ES cells. e, As in d, where the interactions between loci that escape XCI on the wild-type Xi chromosome were divided in three different groups, according to whether pairs of loci belong to the same or different mega-domains. Interactions across the mega-domain boundary only occur on the wild-type Xi chromosome and are lost on the ΔFT Xi chromosome concomitant with loss of transcription of constitutive escapees.