Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells

Abstract Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor (TGF)-β and facilitates tumor progression. We here performed global mapping of accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formalde...

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Autores principales:	Mayu Arase, Yusuke Tamura, Natsumi Kawasaki, Kazunobu Isogaya, Ryo Nakaki, Anna Mizutani, Shuichi Tsutsumi, Hiroyuki Aburatani, Kohei Miyazono, Daizo Koinuma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa345726c13c45a3afa52b00864ccfe5
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spelling	oai:doaj.org-article:aa345726c13c45a3afa52b00864ccfe52021-12-02T11:53:04ZDynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells10.1038/s41598-017-00973-42045-2322https://doaj.org/article/aa345726c13c45a3afa52b00864ccfe52017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00973-4https://doaj.org/toc/2045-2322Abstract Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor (TGF)-β and facilitates tumor progression. We here performed global mapping of accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of regulatory element (FAIRE)-sequencing. TGF-β and Ras altered chromatin accessibility either cooperatively or independently, and AP1, ETS, and RUNX binding motifs were enriched in the accessible chromatin regions of EpH4 and EpRas cells. Etv4, an ETS family oncogenic transcription factor, was strongly expressed and bound to more than one-third of the accessible chromatin regions in EpRas cells treated with TGF-β. While knockdown of Etv4 and another ETS family member Etv5 showed limited effects on the decrease in the E-cadherin abundance and stress fiber formation by TGF-β, gene ontology analysis showed that genes encoding extracellular proteins were most strongly down-regulated by Etv4 and Etv5 siRNAs. Accordingly, TGF-β-induced expression of Mmp13 and cell invasiveness were suppressed by Etv4 and Etv5 siRNAs, which were accompanied by the reduced chromatin accessibility at an enhancer region of Mmp13 gene. These findings suggest a mechanism of transcriptional regulation during Ras- and TGF-β-induced EMT that involves alterations of accessible chromatin, which are partly regulated by Etv4 and Etv5.Mayu AraseYusuke TamuraNatsumi KawasakiKazunobu IsogayaRyo NakakiAnna MizutaniShuichi TsutsumiHiroyuki AburataniKohei MiyazonoDaizo KoinumaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mayu Arase Yusuke Tamura Natsumi Kawasaki Kazunobu Isogaya Ryo Nakaki Anna Mizutani Shuichi Tsutsumi Hiroyuki Aburatani Kohei Miyazono Daizo Koinuma Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells
description	Abstract Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor (TGF)-β and facilitates tumor progression. We here performed global mapping of accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of regulatory element (FAIRE)-sequencing. TGF-β and Ras altered chromatin accessibility either cooperatively or independently, and AP1, ETS, and RUNX binding motifs were enriched in the accessible chromatin regions of EpH4 and EpRas cells. Etv4, an ETS family oncogenic transcription factor, was strongly expressed and bound to more than one-third of the accessible chromatin regions in EpRas cells treated with TGF-β. While knockdown of Etv4 and another ETS family member Etv5 showed limited effects on the decrease in the E-cadherin abundance and stress fiber formation by TGF-β, gene ontology analysis showed that genes encoding extracellular proteins were most strongly down-regulated by Etv4 and Etv5 siRNAs. Accordingly, TGF-β-induced expression of Mmp13 and cell invasiveness were suppressed by Etv4 and Etv5 siRNAs, which were accompanied by the reduced chromatin accessibility at an enhancer region of Mmp13 gene. These findings suggest a mechanism of transcriptional regulation during Ras- and TGF-β-induced EMT that involves alterations of accessible chromatin, which are partly regulated by Etv4 and Etv5.
format	article
author	Mayu Arase Yusuke Tamura Natsumi Kawasaki Kazunobu Isogaya Ryo Nakaki Anna Mizutani Shuichi Tsutsumi Hiroyuki Aburatani Kohei Miyazono Daizo Koinuma
author_facet	Mayu Arase Yusuke Tamura Natsumi Kawasaki Kazunobu Isogaya Ryo Nakaki Anna Mizutani Shuichi Tsutsumi Hiroyuki Aburatani Kohei Miyazono Daizo Koinuma
author_sort	Mayu Arase
title	Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells
title_short	Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells
title_full	Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells
title_fullStr	Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells
title_full_unstemmed	Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells
title_sort	dynamics of chromatin accessibility during tgf-β-induced emt of ras-transformed mammary gland epithelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/aa345726c13c45a3afa52b00864ccfe5
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_version_	1718394885431623680

Dynamics of chromatin accessibility during TGF-β-induced EMT of Ras-transformed mammary gland epithelial cells

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