Fig. 4: Characterization of X-chromosome sex-associated CpGs, genes and pathways.
a Comparison of DNA methylation rates in females and males for the CpGs on the X chromosome, revealing CpGs under XCI significantly (Padj < 10−6) more methylated in females than in males colored red (pattern A), CpGs escaping XCI with methylation rates <0.25 in both sexes with no significant sex difference (Padj > 10−6) colors dark blue (pattern B), CpGs with methylation rates > 0.75 in both sexes with no sex difference (Padj > 10-6) colors orange (pattern C), CpGs significantly more methylated in males than in females (Padj < 10-6) colors purple (pattern D), and CpGs with methylation rates range from 0.25 to 0.75 (Padj > 10-6) colors gray (pattern other). Distribution of methylation patterns in gene regions (b) and CpG regions (c). Significant differences among patterns (chi-square test, two-tailed test, adjusted P < 0.001) exist in all tested gene regions and CpG regions (Supplementary Data 5). KEGG enrichment analysis for genes with pattern A and pattern B in 5UTRs (d) and promoters (e), using hypergeometric test (one-tailed test). The P values without adjustment are shown in (d, e). The P values and adjusted P values are in Supplementary Data 20, 21. The genes with four XCI status categories are labeled in red (XCI), yellow (escape XCI), black (variable XCI), and blue (unknown). The genes labeled in blue in pattern A and B are currently unknown for their XCI status.
