DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells

Adone Mohd-Sarip; Miriam Teeuwssen; Alice G Bot; Maria J De Herdt; Stefan M Willems; Robert J Baatenburg de Jong; Leendert H J Looijenga; Diana Zatreanu; Karel Bezstarosti; Job van Riet; Edwin Oole; Wilfred F J van Ijcken; Harmen J G van de Werken; Jeroen A Demmers; Riccardo Fodde; C Peter Verrijzer

doi:10.1016/j.celrep.2017.06.020

DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells

Adone Mohd-Sarip, Miriam Teeuwssen, Alice G Bot, Maria J De Herdt, Stefan M Willems, Robert J Baatenburg de Jong, Leendert H J Looijenga, Diana Zatreanu, Karel Bezstarosti, Job van Riet, Edwin Oole, Wilfred F J van Ijcken, Harmen J G van de Werken, Jeroen A Demmers, Riccardo Fodde, C Peter Verrijzer

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	61-75
Number of pages	15
Journal	Cell reports
Volume	20
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2017.06.020
Publication status	Published - 5 Jul 2017
Externally published	Yes

Keywords

Acetylation
Carcinoma, Squamous Cell/genetics
Cell Line, Tumor
Cells, Cultured
Chromatin Assembly and Disassembly
Chromosomal Proteins, Non-Histone/metabolism
Epigenesis, Genetic
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
Histones/metabolism
Humans
Intracellular Signaling Peptides and Proteins/metabolism
Methylation
Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism
Mouth Neoplasms/genetics
Protein Processing, Post-Translational
Transcription Factors/metabolism

Access to Document

10.1016/j.celrep.2017.06.020

Cite this

Mohd-Sarip, A., Teeuwssen, M., Bot, A. G., De Herdt, M. J., Willems, S. M., Baatenburg de Jong, R. J., Looijenga, L. H. J., Zatreanu, D., Bezstarosti, K., van Riet, J., Oole, E., van Ijcken, W. F. J., van de Werken, H. J. G., Demmers, J. A., Fodde, R., & Verrijzer, C. 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. https://doi.org/10.1016/j.celrep.2017.06.020

@article{3d5f305618a44509b9cd002f9b0ccef4,

title = "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 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.",

keywords = "Acetylation, Carcinoma, Squamous Cell/genetics, Cell Line, Tumor, Cells, Cultured, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone/metabolism, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Histones/metabolism, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Methylation, Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism, Mouth Neoplasms/genetics, Protein Processing, Post-Translational, Transcription Factors/metabolism",

author = "Adone Mohd-Sarip and Miriam Teeuwssen and Bot, {Alice G} and {De Herdt}, {Maria J} and Willems, {Stefan M} and {Baatenburg de Jong}, {Robert J} and Looijenga, {Leendert H J} and Diana Zatreanu and Karel Bezstarosti and {van Riet}, Job and Edwin Oole and {van Ijcken}, {Wilfred F J} and {van de Werken}, {Harmen J G} and Demmers, {Jeroen A} and Riccardo Fodde and Verrijzer, {C Peter}",

year = "2017",

month = jul,

day = "5",

doi = "10.1016/j.celrep.2017.06.020",

language = "English",

volume = "20",

pages = "61--75",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "1",

}

Mohd-Sarip, A, Teeuwssen, M, Bot, AG, De Herdt, MJ, Willems, SM, Baatenburg de Jong, RJ, Looijenga, LHJ, Zatreanu, D, Bezstarosti, K, van Riet, J, Oole, E, van Ijcken, WFJ, van de Werken, HJG, Demmers, JA, Fodde, R & Verrijzer, CP 2017, 'DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells', Cell reports, vol. 20, no. 1, pp. 61-75. https://doi.org/10.1016/j.celrep.2017.06.020

TY - JOUR

T1 - DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells

AU - Mohd-Sarip, Adone

AU - Teeuwssen, Miriam

AU - Bot, Alice G

AU - De Herdt, Maria J

AU - Willems, Stefan M

AU - Baatenburg de Jong, Robert J

AU - Looijenga, Leendert H J

AU - Zatreanu, Diana

AU - Bezstarosti, Karel

AU - van Riet, Job

AU - Oole, Edwin

AU - van Ijcken, Wilfred F J

AU - van de Werken, Harmen J G

AU - Demmers, Jeroen A

AU - Fodde, Riccardo

AU - Verrijzer, C Peter

PY - 2017/7/5

Y1 - 2017/7/5

N2 - 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.

AB - 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.

KW - Acetylation

KW - Carcinoma, Squamous Cell/genetics

KW - Cell Line, Tumor

KW - Cells, Cultured

KW - Chromatin Assembly and Disassembly

KW - Chromosomal Proteins, Non-Histone/metabolism

KW - Epigenesis, Genetic

KW - Epithelial-Mesenchymal Transition

KW - Gene Expression Regulation, Neoplastic

KW - Histones/metabolism

KW - Humans

KW - Intracellular Signaling Peptides and Proteins/metabolism

KW - Methylation

KW - Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism

KW - Mouth Neoplasms/genetics

KW - Protein Processing, Post-Translational

KW - Transcription Factors/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85021836675&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.06.020

DO - 10.1016/j.celrep.2017.06.020

M3 - Article

C2 - 28683324

SN - 2211-1247

VL - 20

SP - 61

EP - 75

JO - Cell reports

JF - Cell reports

IS - 1

ER -

DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells

Abstract

Keywords

Access to Document

Fingerprint

Cite this