2017-07-05
DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells
Publication
Publication
Cell Reports , Volume 20 - Issue 1 p. 61- 75
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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| , , , , , , , , | |
| doi.org/10.1016/j.celrep.2017.06.020, hdl.handle.net/1765/108075 | |
| Cell Reports | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Mohd-Sarip, A., Teeuwssen, M., Bot, A., de Herdt, M., Willems, S. M., Baatenburg de Jong, R. J., … Verrijzer, P. (2017). DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells. Cell Reports, 20(1), 61–75. doi:10.1016/j.celrep.2017.06.020 |
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