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Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of snail-1

Javaid, S and Zhang, J and Anderssen, E and Black, JC and Wittner, BS and Tajima, K and Ting, DT and Smolen, GA and Zubrowski, M and Desai, R and Maheswaran, S and Ramaswamy, S and Whetstine, JR and Haber, DA (2013) Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of snail-1. Cell Reports. pp. 1679-1689.

Abstract

Epithelial-mesenchymal transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. After Snail-1 induction, epithelial markers were repressed within 6hr, and mesenchymal genes were induced at 24hr. Snail-1 binding to its target promoters was transient (6-48hr) despite continued protein expression, and it was followed by both transient and long-lasting chromatin changes. Pharmacological inhibition of selected histone acetylation and demethylation pathways suppressed the induction as well as the maintenance of Snail-1-mediated EMT. Thus, EMT involves an epigenetic switch that may be prevented or reversed with the use of small-molecule inhibitors of chromatin modifiers. 2013 The Authors

Item Type: Article
Additional Information: pubid: 84 nvp_institute: NIBR contributor_address: (Javaid, Zhang, Anderssen, Black, Wittner, Tajima, Ting, Smolen, Zubrowski, Desai, Maheswaran, Ramaswamy, Whetstine, Haber) Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, United States (Haber) Howard Hughes Medical Institute, Chevy Chase, MD 20815, United States (Zhang) Roswell Park Memorial Cancer Institute, Buffalo, NY 14263, United States (Smolen) Agios Pharmaceuticals, Cambridge, MA 02139, United States (Zubrowski) Novartis Institutes for BioMedical Research, Cambridge, MA 02139, United States (Zhang) The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Shaanxi, China
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21926

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