Fig. 1
Depleting structural maintenance of chromosomes hinge domain containing 1 (SMCHD1) leads to reappearance of S1/S2 compartments in post-X-chromosome inactivation (XCI) cells. a Depth-corrected chromatin interaction maps of the inactive X chromosome (Xi) in wild-type (WT) and Smchd1−/− mouse embryonic fibroblasts (MEFs) binned at 200-kb resolution. Gray-shaded areas, unmappable regions. Also see Supplementary Fig. 2a for the active X chromosome (Xa) maps. b The corresponding Pearson’s correlation maps of the Xi in WT and Smchd1−/− MEFs binned at 200-kb resolution. Also see Supplementary Fig. 2a for the Xa maps. c Principal component 1 (PC1) and PC2 values of the Xi in WT and Smchd1−/− MEFs. Regions with positive PC1 values on the Smchd1−/− Xi represent the S1 (Xist-rich) compartment (red). Also shown are Xi-specific H3K4me3 chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) peaks (Xmus, GSE33823), Xist CHART-seq (capture hybridization analysis of RNA targets with deep sequencing) (GSE48649), H3K27me3 ChIP-seq (GSE33823), H2AK119ub ChIP-seq (GSE107217), and SMCHD1 DNA adenine methyltransferase identification by sequencing (DamID-seq) (GSE99991) profiles in WT MEFs. Xist, H3K27me3, and H2AK119ub profiles were displayed as heatmaps, with scale bars shown below the tracks. Also see Supplementary Fig. 2b for the PCs of the Xa. d PC1 values of the Xi in Smchd1−/− MEFs and embryoid bodies formed after 4 days of differentiation of female WT mouse embryonic stem cells (D4 EB, early XCI) (GSE99991). Regions with positive PC1 values represent the S1 (Xist-rich) compartment (red). e Comparison of the compartment profile (PC1) (top) of the Smchd1−/− Xi and the topologically associated domain (TAD) insulation profiles (bottom) of the WT (black) and Smchd1−/− Xi (red) at two representative X-linked regions. TADs (as defined in Dixon et al.2) were depicted as blue bars between plots and as dashed lines (TAD boundaries) within each plot. Green dashed lines, the borders of S1/S2 compartments. Yellow-shaded area: Dxz4. Gray-shaded areas, unmappable regions. f Box plots comparing the insulation scores of the TAD boundaries associated with borders of S1/S2 compartments (green) and the other TAD boundaries (gray) on the Xi. Note that lower insulation scores indicate stronger insulation effects. P values are given by the Wilcoxon’s rank-sum test. NS, not significant (P > 0.05). *P = 0.0018; **P = 0.0015. Midline, median. Top and bottom of the box, first and third quartile. Whiskers, extension from the top or bottom to the furthest datum within 1.5 times the interquartile range
