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

Accession Number: GSE97839 Platform: GPL16791: Illumina HiSeq 2500 (Homo sapiens) Organism: Homo sapiens Published on 2017-07-05 Summary: 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. Overall Design: Examination of NURD binding with loss of NURD subunit DOC1. Contact: Name: C. Peter Verrijzer Organization: Erasmus MC Deparment: Department of Biochemistry Address: Dr Molewaterplein 50 Rotterdam Netherlands Email: [email protected] Phone: +31-104087461 Organization: GEO Address: US

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

Accession Number: GSE97839 Platform: GPL16791: Illumina HiSeq 2500 (Homo sapiens) Organism: Homo sapiens Published on 2017-07-05 Summary: 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. Overall Design: Examination of NURD binding with loss of NURD subunit DOC1. Contact: Name: C. Peter Verrijzer Organization: Erasmus MC Deparment: Department of Biochemistry Address: Dr Molewaterplein 50 Rotterdam Netherlands Email: [email protected] Phone: +31-104087461 Organization: GEO Address: US