Fig. 1

Identifying differentially methylated CpG sites (DMCs) across ovarian cancer cell lines with progressive epithelial–mesenchymal transition (EMT) phenotypes. a Diagram illustrates the EMT/mesenchymal–epithelial transition (MET) models used: 30 ovarian cancer cell lines with progressive EMT scores and OVCA429 GRHL2-knockdown model for Methylation 450K array; four-cell-line model (PEO1, OVCA429, SKOV3, HEYA8) and OVCA429 GRHL2-knockdown model for histone chromatin immunoprecipitation (ChIP)-sequencing; OVCA429 shGRHL2 Tet-GRHL2* (rescue) and HEYA8 Tet-GRHL2 for epigenetic drug treatment assays. b Bar charts indicate the percentage of EMT+ DMCs, EMT− DMCs, and non EMT-correlated CpG sites identified and their respective distribution in genome-wide CpG islands. EMT+ refers to a positive correlation with EMT; EMT− refers to a negative correlation with EMT. c Bar charts showing EMT score (top); frequency of methylated and unmethylated EMT-correlated DMCs (middle); and frequency of methylated and unmethylated EMT-correlated DMCs |ρ| > 0.5 (bottom) in 30 tested cell lines (x-axis). d Heatmaps of EMT signature genes with DMCs in promoter regions (left) and those with DMCs in gene bodies (right) showing CpG methylation level (blue = low; yellow = high) and the corresponding gene expression (red = high; blue = low) in ovarian cancer cell lines with progressive EMT scores (bar chart). Only genes with strong differential expression in correlation with EMT (|ρ| > 0.5) were shown. e Known motif enrichment analysis and de novo motif discovery showing DNA-binding motifs of transcription factors that are enriched at the DMCs, such as that of GRHL2 in EMT+ DMCs (ρ > 0.5, left panel) and CTCFL in EMT− DMCs (ρ <−0.5, right panel). EOC, epithelial ovarian carcinoma