ERK signalling modulates epigenome to drive epithelial to mesenchymal transition
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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
Vijay K. Tiwari, email: email@example.com
Keywords: EMT, ERK, epigenetics, transcription factors, gene regulation
Received: December 15, 2016 Accepted: February 06, 2017 Published: March 23, 2017
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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