DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells
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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-07-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717308173 |
| _version_ | 1811278909044424704 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Adone Mohd-Sarip |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T00:45:15Z |
| format | Article |
| id | doaj.art-388a23c8a0fc482fa04851442525be89 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T00:45:15Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-388a23c8a0fc482fa04851442525be892022-12-22T03:10:02ZengElsevierCell Reports2211-12472017-07-01201617510.1016/j.celrep.2017.06.020DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer CellsAdone Mohd-Sarip0Miriam Teeuwssen1Alice G. Bot2Maria J. De Herdt3Stefan M. Willems4Robert J. Baatenburg de Jong5Leendert H.J. Looijenga6Diana Zatreanu7Karel Bezstarosti8Job van Riet9Edwin Oole10Wilfred F.J. van Ijcken11Harmen J.G. van de Werken12Jeroen A. Demmers13Riccardo Fodde14C. Peter Verrijzer15Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7BL, UK, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Pathology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Biochemistry, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the NetherlandsDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Pathology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Biochemistry, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsProteomics Centre, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsCancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsCenter for Biomics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsCenter for Biomics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsCancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsProteomics Centre, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Pathology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsDepartment of Biochemistry, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the NetherlandsThe 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.http://www.sciencedirect.com/science/article/pii/S2211124717308173chromatinepigeneticsoral cancerDOC1/CDK2AP1NURDCHD4epithelial-mesenchymal transitionSWI/SNFPolycomb |
| spellingShingle | 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 DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells Cell Reports chromatin epigenetics oral cancer DOC1/CDK2AP1 NURD CHD4 epithelial-mesenchymal transition SWI/SNF Polycomb |
| title | DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells |
| title_full | DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells |
| title_fullStr | DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells |
| title_full_unstemmed | DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells |
| title_short | DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells |
| title_sort | doc1 dependent recruitment of nurd reveals antagonism with swi snf during epithelial mesenchymal transition in oral cancer cells |
| topic | chromatin epigenetics oral cancer DOC1/CDK2AP1 NURD CHD4 epithelial-mesenchymal transition SWI/SNF Polycomb |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717308173 |
| work_keys_str_mv | AT adonemohdsarip doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT miriamteeuwssen doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT alicegbot doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT mariajdeherdt doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT stefanmwillems doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT robertjbaatenburgdejong doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT leenderthjlooijenga doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT dianazatreanu doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT karelbezstarosti doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT jobvanriet doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT edwinoole doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT wilfredfjvanijcken doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT harmenjgvandewerken doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT jeroenademmers doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT riccardofodde doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells AT cpeterverrijzer doc1dependentrecruitmentofnurdrevealsantagonismwithswisnfduringepithelialmesenchymaltransitioninoralcancercells |