DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition i
In: Cell Reports vol. 20 no. 1, pp. 61-75, 2017
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Zugriff:
The Nucleosome Remodeling and Deacetylase (NURD) complex is a key regulator of cell differentiation that has also been implicated in tumorigenesis. Loss of the NURD subunit Deleted in Oral Cancer 1 (DOC1) is associated with human oral squamous cell carcinomas (OSCCs). Here, we show that restoration of DOC1 expression in OSCC cells leads to a reversal of epithelial-mesenchymal transition (EMT). This is caused by the DOC1-dependent targeting of NURD to repress key transcriptional regulators of EMT. NURD recruitment drives extensive epigenetic reprogramming, including eviction of the SWI/SNF remodeler, formation of inaccessible chromatin, H3K27 deacetylation, and binding of PRC2 and KDM1A, followed by H3K27 methylation and H3K4 demethylation. Strikingly, depletion of SWI/SNF mimics the effects of DOC1 re-expression. Our results suggest that SWI/SNF and NURD function antagonistically to control chromatin state and transcription. We propose that disturbance of this dynamic equilibrium may lead to defects in gene expression that promote oncogenesis.
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DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition i
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Autor/in / Beteiligte Person: | Mohd-Sarip, A. (Adone) ; Teeuwssen, M. (Miriam) ; Bot, A.G. (Alice) ; Herdt, M.J. (Maria) de ; Willems, S.M. (Stefan Martin) ; Baatenburg de Jong, R.J. (Robert Jan) ; Looijenga, L.H.J. (Leendert) ; Zatreanu, D. (Diana) ; Bezstarosti, K. (Karel) ; Riet, J. (Job) van ; Oole, E. (Edwin) ; IJcken, W.F.J. (Wilfred) van ; Werken, H.J.G. (Harmen) van de ; Demmers, J.A.A. (Jeroen) ; Fodde, R. (Riccardo) ; Verrijzer, C.P. (Peter) |
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Zeitschrift: | Cell Reports vol. 20 no. 1, pp. 61-75, 2017 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
DOI: | 10.1016/j.celrep.2017.06.020 |
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