Sox4 is a master regulator of epithelial-mesenchymal transition (EMT) by controlling Ezh2 expression and epigenetic reprogramming
Gene expression profiling has uncovered the transcription factor Sox4 with up-regulated activity during TGFß-induced EMT in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, while forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2. Overall design: Our Dataset comprises of 12 ChIP-seq samples using chromatin from NMuMG cells which was immunoprecipitated using H3K27me3-specific antibody during TGFß-induced EMT (2ng/ml) at 6 different stages (day 0, 1, 4, 7, 10, 20).