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Volume 6 Supplement 6

Beyond the Genome 2012

Epigenetic reprogramming in the epithelial-to-mesenchymal transition

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The epithelial-to-mesenchymal transition (EMT) is a cellular dedifferentiation process that is critical to development, wound healing and metastasis. Like other cell state transitions, such as differentiation, EMT is accompanied by genome-wide epigenetic reprogramming. However, the relationship between reprogramming and functional changes in the cell is poorly understood. In an A549 non-small cell lung cancer EMT model system we observed changes in chromatin state between epithelial and mesenchymal states. Multivariate analyses were applied to paired (epithelial and mesenchymal) ChIP-seq data for 18 histone modifications/variants and expression microarray data. We observed epigenetic co-regulation of genes associated with EMT, as well as their proximal enhancers. We also observed epigenetic activation or repression of functionally distinct sets of enhancers. These genes and enhancers are regulated and bound by a small set of transcription factors, specifically AP-1, NF-κB and c-Myc. These transcription factors themselves also a show an epigenetic profile similar to the EMT-related genes. Together, these observations suggest a chromatin-mediated transcriptional feedback mechanism that establishes and maintains the phenotypic switch.

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Correspondence to Stephen Hoang.

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Stephen Hoang, Marcin Cieślik contributed equally to this work.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hoang, S., Cieślik, M., Chodaparambil, S. et al. Epigenetic reprogramming in the epithelial-to-mesenchymal transition. BMC Proc 6, O28 (2012). https://doi.org/10.1186/1753-6561-6-S6-O28

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Keywords

  • Lung Cancer
  • Chromatin State
  • Expression Microarray Data
  • Phenotypic Switch
  • Epigenetic Reprogram