Dynamic Chromatin Modification Sustains Epithelial-Mesenchymal Transition following Inducible Expression of Snail-1

Sarah Javaid; Jianmin Zhang; Endre Anderssen; Josh C. Black; Ben S. Wittner; Ken Tajima; David T. Ting; Gromoslaw A. Smolen; Matthew Zubrowski; Rushil Desai; Shyamala Maheswaran; Sridhar Ramaswamy; Johnathan R. Whetstine; Daniel A. Haber

doi:10.1016/j.celrep.2013.11.034

Cell Reports (Dec 2013)

Dynamic Chromatin Modification Sustains Epithelial-Mesenchymal Transition following Inducible Expression of Snail-1

Sarah Javaid,
Jianmin Zhang,
Endre Anderssen,
Josh C. Black,
Ben S. Wittner,
Ken Tajima,
David T. Ting,
Gromoslaw A. Smolen,
Matthew Zubrowski,
Rushil Desai,
Shyamala Maheswaran,
Sridhar Ramaswamy,
Johnathan R. Whetstine,
Daniel A. Haber

Affiliations

Sarah Javaid: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Jianmin Zhang: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Endre Anderssen: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Josh C. Black: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Ben S. Wittner: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Ken Tajima: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
David T. Ting: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Gromoslaw A. Smolen: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Matthew Zubrowski: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Rushil Desai: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Shyamala Maheswaran: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Sridhar Ramaswamy: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Johnathan R. Whetstine: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA
Daniel A. Haber: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA

DOI: https://doi.org/10.1016/j.celrep.2013.11.034
Journal volume & issue: Vol. 5, no. 6
pp. 1679 – 1689

Abstract

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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 6 hr, and mesenchymal genes were induced at 24 hr. Snail-1 binding to its target promoters was transient (6–48 hr) 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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