Fig. 2: Maternal allele-specific enrichment of EHMT2 at PWS-IC that is independent from DNA methylation.

a Schematic diagram of PWS-associated imprinted ___domain on chromosome 15 (blue allele; paternally expressed genes, gray allele; biallelic expressed gene, BP; break point found in PWS patient with 15q11.2-q13 deletion. Green bar; CGIs). b Schematic diagram of primer binding region (a,b,c within PWS imprinting center. c–e ChIP–qPCR quantification of EHMT2 and H3K9me2 on PWS-IC in human fibroblasts derived from Angelman syndrome (AS) and PWS patients (AS; paternal 15q11.2-q13 deletion, PWS; maternal 15q11.2-q13 deletion, Ctr; Control). H3K9me2 is significantly abundant on PWS-IC of maternal chromosome compared to AS and Control after treatment of 5-Aza as a DNMT1 inhibitor. (One-way ANOVA test followed by Dunnett’s multiple comparison test; Adj p-value is indicated in graph; 50th percentile (median value, line), 25th to 75th percentiles of dataset (box), 5th and 95th percentile (Whiskers)). f Schematic diagram of primer binding site on CGI in PWS-IC for bisulfite genomic sequencing. g Comparison of DNA methylation in AS (paternal CGI), PWS type I deletion, and Uniparental disomy (UPD) (maternal CGI), and a control (gray; unmethylated CpG, black; methylated CpG). h Quantification of DNA methylation level on PWS-IC (Two-way ANOVA test followed by Tukey’s multiple comparison test; ^****p < 0.0001). Data are presented as mean ± SEM. i Genome-wide methylation analysis shows that allele-specific DNA methylation is shown in PWS-IC but not other CGIs. Heat map depicts average methylation scores (0; unmethylated CpG, 1; methylated CpG). Source data are provided as a Source Data file.