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

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

doi:10.1016/j.celrep.2017.06.020

Cited by 53 publications

(61 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SWI/SNF core subunits and RNA processing proteins were shared among the wild-type and SCCOHT SWI/SNF complexes (Figure 7). The wild-type SWI/SNF complex showed interactions with the NuRD chromatin remodeling and HDAC complex, consistent with previous reports that the NuRD complex interacts with SWI/SNF and shows functional antagonism in embryonic stem cells 55,56 and in oral squamous cell carcinoma cells 57 . The absence of SCCOHT SWI/SNF interactions with NuRD warrants future investigation of potential roles of NuRD in SCCOHT cells.…”

Section: Sccoht Residual Swi/snf Complex Shows Reduced Interactions Wsupporting

confidence: 91%

Novel functional insights revealed by distinct protein-protein interactions of the residual SWI/SNF complex in SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type

Raupach

Garcia-Mansfield

Sharma

et al. 2019

Preprint

View full text Add to dashboard Cite

Chromatin remodeling plays a critical role in tumor suppression as demonstrated by 20% of human cancers bearing inactivating mutations in SWI/SNF chromatin remodeling complex members. Mutations in different SWI/SNF subunits drive a variety of adult and pediatric tumor types, including non-small cell lung cancers, rhabdoid tumors, medulloblastomas, and ovarian cancers. Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is an aggressive subtype of ovarian cancer occurring in young women. Nearly all (>98%) SCCOHTs have inactivating mutations in SMARCA4, which encodes 1 of 2 mutually exclusive catalytic subunits of the SWI/SNF complex. Less than half of SCCOHT patients survive 5 years despite aggressive surgery and multimodal chemotherapy. Empirical support for effective SCCOHT treatments is scarce, in part because of the poor understanding of SCCOHT tumorigenesis. To gain insight into the functional consequences of SWI/SNF subunit loss, we defined SWI/SNF composition and its protein-protein interactions (PPIs) by immunoprecipitation and mass spectrometry (IP-MS) of SWI/SNF subunits in 3 SCCOHT cell lines. Comparing these results to a cell line containing a wild-type SWI/SNF complex, the interaction of most canonical core SWI/SNF subunits was observed in all SCCOHT cell lines at a lower abundance. The SCCOHT SWI/SNF also lacked ATPase module subunits and showed a drastic reduction in PBAF-specific subunit interactions. The wild-type and SCCOHT SWI/SNF subunits immunoprecipitated a shared set of 26 proteins, including core SWI/SNF subunits and RNA processing proteins. We observed 131 proteins exclusively interacting with the wild-type SWI/SNF complex including isoform-specific SWI/SNF subunits, members of the NuRD complex, and members of the MLL3/4 complex. We observed 60 PPIs exclusive to the SCCOHT residual SWI/SNF shared in at least 2 of the 3 SCCOHT cell lines, including many proteins involved in RNA processing. Differential interactions with the residual SWI/SNF complex in SCCOHT may further elucidate altered functional consequences of SMARCA4 mutations in these tumors as well as identify synthetic lethal targets that translate to other SWI/SNF-deficient tumors.Introduction:

show abstract

Section: Sccoht Residual Swi/snf Complex Shows Reduced Interactions Wsupporting

confidence: 91%

Novel functional insights revealed by distinct protein-protein interactions of the residual SWI/SNF complex in SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type

Raupach

Garcia-Mansfield

Sharma

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Several studies, in both yeast and mammalian cells, point to cooperative or opposing activities of certain CRs (Gkikopoulos et al, 2011;Mohd-Sarip et al, 2017;Morris et al, 2014;Parnell et al, 2015;Rawal et al, 2018;Tomar et al, 2009;Yen et al, 2012).It is thus of interest to learn how the activities of the complete set of these enzymes are intertwined. Since RSC is the only yeast CR essential for cell viability, the activities of all other CRs in live cells have been studied predominantly by the use of deletion mutants.…”

Section: Introductionmentioning

confidence: 99%

Opposing chromatin remodelers control transcription initiation frequency and start site selection

Kubik¹,

Challal

Bruzzone³

et al. 2019

Preprint

View full text Add to dashboard Cite

Precise nucleosome organization at eukaryotic promoters is thought to be generated by multiple chromatin remodeler (CR) enzymes and to affect transcription initiation. Using an integrated analysis of chromatin remodeler binding and nucleosome displacement activity following rapid remodeler depletion, we investigate the interplay between these enzymes and their impact on transcription in budding yeast. We show that many promoters are acted upon by multiple CRs that operate either cooperatively or in opposition to position the key transcription start site-associated +1 nucleosome. Functional assays suggest that +1 nucleosome positioning often reflects a trade-off between maximizing RNA Polymerase II recruitment and minimizing transcription initiation at incorrect sites.Finally, we show that nucleosome movement following CR inactivation usually results from the activity of another CR and that in the absence of any remodeling activity +1 nucleosomes maintain their positions. Our results provide a detailed picture of fundamental mechanisms linking promoter nucleosome architecture to transcription initiation.

show abstract

“…It was recently demonstrated that this is achieved in both ES cells and B‐cell progenitors by restricting access of transcription factors to regulatory sequences (Liang et al , ; Loughran et al , ; Bornelöv et al , ). Additionally, aberrations in expression levels of NuRD component proteins are increasingly being linked to cancer progression (Lai & Wade, ; Mohd‐Sarip et al , ).…”

Section: Introductionmentioning

confidence: 99%

The Nucleosome Remodelling and Deacetylation complex suppresses transcriptional noise during lineage commitment

et al. 2019

View full text Add to dashboard Cite

Multiprotein chromatin remodelling complexes show remarkable conservation of function amongst metazoans, even though components present in invertebrates are often found as multiple paralogous proteins in vertebrate complexes. In some cases, these paralogues specify distinct biochemical and/or functional activities in vertebrate cells. Here, we set out to define the biochemical and functional diversity encoded by one such group of proteins within the mammalian Nucleosome Remodelling and Deacetylation (Nu RD ) complex: Mta1, Mta2 and Mta3. We find that, in contrast to what has been described in somatic cells, MTA proteins are not mutually exclusive within embryonic stem (ES) cell Nu RD and, despite subtle differences in chromatin binding and biochemical interactions, serve largely redundant functions. ES cells lacking all three MTA proteins exhibit complete Nu RD loss of function and are viable, allowing us to identify a previously unreported function for Nu RD in reducing transcriptional noise, which is essential for maintaining a proper differentiation trajectory during early stages of lineage commitment.

show abstract

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

Cited by 53 publications

References 45 publications

Novel functional insights revealed by distinct protein-protein interactions of the residual SWI/SNF complex in SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type

Novel functional insights revealed by distinct protein-protein interactions of the residual SWI/SNF complex in SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type

Opposing chromatin remodelers control transcription initiation frequency and start site selection

The Nucleosome Remodelling and Deacetylation complex suppresses transcriptional noise during lineage commitment

Contact Info

Product

Resources

About