Fig. 4: The SD-domain genes are preferentially reactivated and lose repressive Xi signatures in SmcHD1-mutant NPCs.

a, Comparison of Xi probability of X-linked gene expression ((mus-Xi reads)/(mus-Xi reads + cas-Xa reads); 0 and 0.5 represent fully silenced and reactivated Xi states, respectively), Xist RNA enrichment by CHART-seq and H3K27me3 and H3K4me3-ChIP–seq (ref. ¹¹) on the Xi in WT and SmcHD1-mutant (KO) NPCs. BrdU-IP RT of the NSC Xi (B6-Xi) is shown for comparison. Class I (SmcHD1-sensitive), class II (partially SmcHD1-sensitive), class III (SmcHD1-insensitive) and unclassified genes are based on expression analysis by Wang et al.¹¹. Bin sizes are shown in parentheses. Upper and lower panels show the entire Xi and the magnified views of four representative SD-domain regions, respectively. Colored bars, RT classes. b, Comparison of Xi probability of 225 X-linked gene expression between RT classes in WT and KO NPCs. Escapees in NPCs identified by Wang et al.¹¹ were removed before the analysis. N, the number of X-linked genes in each class. P values were obtained from one-sided paired Wilcoxon signed-rank test. c–e, Comparison of Xist (c), H3K27me3 (d) and H3K4me3 (e) enrichment on the SmcHD1-KO versus WT Xi among RT classes. N, the number of genomic bins in each class. The log₂(fold change) is shown. P values in c–e were obtained from a one-sided Wilcoxon signed-rank test with the Bonferroni correction.

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