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In normal intestine, WNT2 expression is repressed by PRC2-induced H3K27me3 histone modification of WNT2 proximal promoter. By unknown mechanisms, PRC2's repressive function on WNT2 expression is inhibited and WNT2 expression is de-repressed. Subsequently, Wnt2 activates canonical Wnt signaling during intestinal tumorigenesis, which leads to maintenance of hyperactivation of Wnt/β-catenin signaling for CRC cell proliferation.
