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. 2017 Apr 26;7:1166. doi: 10.1038/s41598-017-00973-4

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Effect of Etv4/5 siRNAs on the global chromatin accessibility. (A) Scatter plots showing the effect of TGF-β (X-axis) and Etv4/5 siRNAs (Y-axis) on the genome-wide chromatin accessibility determined by FAIRE-seq. Note that there was a significant correlation between the effect of two different siRNA sets (r = 0.51, p < 2.2e-16, Supplementary Fig. S7). (B) Enrichment of ETS binding motif in the FAIRE-positive regions of EpRas cells treated by TGF-β and siRNAs as indicated. (C) A schematic model for regulation of EMT-related gene expression through the differential expression of transcription factors and alteration of chromatin accessibility. In the process of EMT, chromatins are gradually closed by Ras and TGF-β at the Cdh1/E-cadherin gene locus. In contrast, upregulated genes are regulated by a variety of mechanisms. The Fn1/fibronectin gene locus is open irrespective of Ras and TGF-β treatment, while Cdh2/N-cadherin gene locus becomes accessible upon Ras transformation, and the Mmp13 gene locus becomes accessible upon Ras transformation and TGF-β stimulation. Differentially expressed transcription factors, Etv4 and Etv5, are responsible for a subset of EMT-related changes in gene expression partially through the alteration of chromatin accessibility.