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DOC1-dependent recruitment of NURD reveals antagonism with SWI/SNF during epithelial-mesenchymal transition in oral cancer cells.

ABSTRACT: 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 DOC1 is associated with human oral squamous cell carcinomas (OSCC). 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 recruitment of NURD to repress the Twist master regulators of EMT. NURD recruitment drives extensive epigenetic reprogramming, including eviction of the SWI/SNF remodeler, formation of inaccessible chromatin, H3K27 deacetylation, recruitment 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. We propose that disturbance of this dynamic equilibrium may lead to defects in gene expression that drive human cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97839 | GEO | 2017/07/05

SECONDARY ACCESSION(S): PRJNA382995

REPOSITORIES: GEO

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The impact of SWI/SNF and NuRD inactivation on gene expression is tightly coupled with levels of RNA Polymerase II occupancy at promoters

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