Oncotarget

Research Papers:

ERK signalling modulates epigenome to drive epithelial to mesenchymal transition

Mohit Navandar, Angela Garding, Sanjeeb Kumar Sahu, Abhijeet Pataskar, Sandra Schick and Vijay K. Tiwari _

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Oncotarget. 2017; 8:29269-29281. https://doi.org/10.18632/oncotarget.16493

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Abstract

Mohit Navandar1,*, Angela Garding1,*, Sanjeeb Kumar Sahu1, Abhijeet Pataskar1, Sandra Schick1, Vijay K. Tiwari1

1Institute of Molecular Biology (IMB), Mainz, Germany

*These authors have contributed equally to this work

Correspondence to:

Vijay K. Tiwari, email: v.tiwari@imb-mainz.de

Keywords: EMT, ERK, epigenetics, transcription factors, gene regulation

Received: December 15, 2016     Accepted: February 06, 2017     Published: March 23, 2017

ABSTRACT

The series of events that allow the conversion from adherent epithelial cells into migratory cells is collectively known as epithelial-mesenchymal transition (EMT). EMT is employed during embryonic development such as for gastrulation and neural crest migration and is misused in diseases, such as cancer metastasis. ERK signalling is known to be essential for EMT, however its influence on the epigenetic and transcriptional programme underlying EMT is poorly understood. Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene expression in mammary epithelial cells undergoing EMT, we found that ERK signalling is essential for the epigenetic reprogramming underlying hallmark gene expression and phenotypic changes of EMT. We show that the chemical inhibition of Erk signalling during EMT prevents the loss and gain of the H3K27ac mark at regulatory regions of epithelial and mesenchymal genes, respectively, and results in a transcriptome and epigenome closer to those of epithelial cells. Further computational analyses identified a distinct set of transcription factor motifs enriched at distal regulatory regions that are epigenetically remodelled by ERK signalling. Altogether, our findings reveal an ERK-dependent epigenetic remodelling of regulatory elements that results in a gene expression programme essential for driving EMT.


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