title: Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming.
abstract: Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (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, whereas 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.
authors.affiliation: Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Neha
authors.initials: N
authors.lastname: Tiwari
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Tiwari
authors.forename: Lorenz
authors.initials: L
authors.lastname: Waldmeier
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Balwierz
authors.forename: Phil
authors.initials: P
authors.lastname: Arnold
authors.forename: Mikhail
authors.initials: M
authors.lastname: Pachkov
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meyer-Schaller
authors.forename: Dirk
authors.initials: D
authors.lastname: Schübeler
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2