EED regulates epithelial–mesenchymal transition of cancer cells induced by TGF-β

• EED is one of the core components of PRC2 that catalyzes histone H3K27 methylation.
• EED is only one PRC2 core member whose expression was increased in TGF-β-induced EMT.
• EED knockdown inhibited TGF-β-dependent expression changes of EMT-related genes.
• EED regulates EZH2 recruitment and H3K27 methylation on the EMT-related genes.
• EED is required for TGF-β-induced EMT of cancer cells.

Histone methylation is involved in various biological and pathological processes including cancer development. In this study, we found that EED, a component of Polycomb repressive complex-2 (PRC2) that catalyzes methylation of lysine 27 of histone H3 (H3K27), was involved in epithelial–mesenchymal transition (EMT) of cancer cells induced by Transforming Growth Factor-beta (TGF-β). The expression of EED was increased during TGF-β-induced EMT and knockdown of EED inhibited TGF-β-induced morphological conversion of the cells associated with EMT. EED knockdown antagonized TGF-β-dependent expression changes of EMT-related genes such as CDH1, ZEB1, ZEB2 and microRNA-200 (miR-200) family. Chromatin immunoprecipitation assays showed that EED was implicated in TGF-β-induced transcriptional repression of CDH1 and miR-200 family genes through the regulation of histone H3 methylation and EZH2 occupancies on their regulatory regions. Our study demonstrated a novel role of EED, which regulates PRC2 activity and histone methylation during TGF-β-induced EMT of cancer cells.