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 natio glide on eyeshadow stick 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 cubs foam finger 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.